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103 57 blood pressure: Blood Pressure 103 over 57

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Blood pressure – Better Health Channel

Blood pressure is the pressure of the blood in the arteries as it is pumped around the body by the heart. Blood pressure does not stay the same all the time. It changes to meet your body’s needs. It is affected by various factors, including body position, breathing, emotional state, exercise and sleep.  

If blood pressure remains high, it can lead to serious problems like heart attack, stroke, heart failure or kidney disease. The medical name for persistently high blood pressure is hypertension and the medical name for low blood pressure is hypotension. 

How blood pressure is measured

It is best to measure blood pressure when you are relaxed and sitting. Blood pressure is usually measured by wrapping an inflatable pressure cuff around your upper arm. (This cuff is part of a machine called a sphygmomanometer.) 

Blood pressure is recorded as two numbers, such as 120/80. The larger number indicates the pressure in the arteries as the heart pumps out blood during each beat. This is called the systolic blood pressure. 

The lower number indicates the pressure as the heart relaxes before the next beat. This is called the diastolic blood pressure. Both are measured in units called millimetres of mercury (mmHg).

Variations in blood pressure

Your blood pressure changes to meet your body’s needs. If a reading is high, your doctor may measure your blood pressure again on several separate occasions to confirm the level. 

Your doctor may also recommend that you measure your blood pressure at home or have a 24-hour recording with a monitoring device. 

Blood pressure readings

What is considered a healthy blood pressure varies from person to person. Your doctor will advise you about what your ideal blood pressure is based on your circumstances, including your overall health.

The following figures should only be used as a guide:

Meaning Top number (systolic) mm Hg   Bottom number (diastolic) mm Hg
 Low Less than 90 Less than 60
 Optimal   Less than 120 Less than 80
 Normal  120 to 129  80 to 84
 High-normal   130 to 139 85 to 89
 High  Greater than 140 Greater than 90

High blood pressure usually does not give warning signs. You can have high blood pressure and feel perfectly well. The only way to find out if your blood pressure is high is to have it checked regularly by your doctor.

Low blood pressure is relative – what is low for one person may be okay for another – and is only considered a problem if it has a negative impact on your body or it affects the way you feel.

Get regular blood pressure checks

If your blood pressure is in the healthy range and you have no other risk factors for cardiovascular disease, and no personal or family history of high blood pressure, it is still important to have a check at least every two years. Your doctor can also check your blood pressure   during routine visits.

If your blood pressure is ‘high–normal’ (or higher – for example 140/95), or if you have other risk factors for cardiovascular disease, such as a personal or family history of high blood pressure, stroke or heart attack, it is best to have it checked more frequently – such as every 6 to 12 months or as directed by your doctor. Ask your doctor for advice.

Managing high blood pressure

If your blood pressure remains high, it can lead to serious health problems. You will be more at risk of these problems if you:

Lifestyle changes are very important to help manage high blood pressure and lower your risk of cardiovascular disease. Suggestions include: 

  • Enjoy a wide variety of foods
  • Decrease your salt (sodium) intake. (Salt is a mineral and is made up of sodium and chloride, but it’s the sodium in salt that is bad for your health. Although health professionals talk about salt, it is the sodium that is listed on food labels in supermarkets that it is important to keep track of.)
  • Achieve and maintain a healthy weight.
  • Be moderately physically active for 30 to 45 minutes per day, five days or more in the week. Alternatively, aim for vigorous activity (activity that makes you huff and puff) for 15 to 30 minutes, five or more days of the week.
  • Limit your alcohol intake to no more than 10 standard drinks a week.
  • Quit smoking.

Some people may also need medicine to manage high blood pressure, but it is still important for them to make lifestyle changes too.

High blood pressure and daily activity

Check with your doctor before starting a new activity or increasing your level or intensity. Be active safely. – Build up your levels of activity gradually.

Try to do at least 30 to 45 minutes of moderate-intensity physical activity on most, if not all, days of the week. This can be done in bouts of 10 minutes or longer, if that is more convenient.

Physical activity is any form of bodily movement performed by our large muscle groups. Moderate-intensity physical activity (energetic activity that doesn’t make you overly breathless), such as brisk walking or cycling, is enough to provide health benefits.

Walking is a great activity for all ages. You may like to join one of the Heart Foundation’s community walking groups. 

Some types of exercises, such as body presses and lifting heavy weights, can raise your blood pressure. Avoid these if you have high blood pressure. 

High blood pressure and diet

Following a diet that emphasises the intake of vegetables, fruits and whole grains, including low-fat dairy products, such as in the Dietary Approaches to Stop Hypertension (DASH) diet, may be combined with exercise and weight loss to maximise blood pressure reduction.

Healthy eating is important in managing high blood pressure and reducing your risk of heart disease. 

Follow these heart healthy eating patterns recommended by the Heart Foundation:

  • Eat plenty of fruit, vegetables and wholegrains.
  • Include a variety of healthy protein sources – especially fish and seafood, legumes (such as beans and lentils), nuts and seeds. Smaller amounts of eggs and lean poultry can also be included in a heart healthy diet. If choosing red meat, make sure it is lean and limit to 1-3 times a week.
  • Consume unflavoured milk, yoghurt and cheese. If you have high cholesterol, choose reduced fat varieties.
  • Make healthy fat choices with nuts, seeds, avocados, olives and their oils for cooking.
  • Add herbs and spices to flavour foods, instead of adding salt.
  • Drink mainly water.

Salt intake and high blood pressure

Reducing the amount of salt (sodium) you eat can also help to manage or even avoid high blood pressure. To help reduce your salt intake: 

  • Ensure your diet consists of wholefoods including – vegetables, fruits, wholegrains, lean meat and poultry, fish and seafood, legumes, unsalted nuts and seeds.
  • Avoid packaged and processed foods (such as pizzas, pastries, biscuits and take away foods) that are high in salt. You can’t see the salt in these foods, so you don’t know how much salt you are having. Get into the habit of checking food labels.
  • Choose low-salt (less than 120mg sodium per 100g) food where possible. If you can’t find low-salt products, those with moderate amounts of salt (less than 400mg sodium per 100g) are ok too. Another simple alternative is to look for labels with ‘low salt’, ‘salt reduced’ or ‘no added salt.
  • Avoid adding salt to cooking or at the table – flavour meals with herbs and spices instead.

Medications for high blood pressure

There is a large variety of medicines available to lower and manage high blood pressure. Your doctor may call them ‘antihypertensives’, (which basically means ‘anti’ – against and ‘hypertensive’ – high blood pressure).

These medications do not cure high blood pressure, but they do help manage it. Once you start to take medicines to manage your blood pressure, you may need to take them for the rest of your life. However, the dose of these medicines may change over time.

If you need to take medication, your doctor will advise you on the correct type and dose. Two or more different medications are often needed to manage blood pressure.

Make sure you take your medicines regularly. Some things that may help you remember to take them include: 

  • Building them into your daily routine by taking them at the same time each day.  
  • Keeping them somewhere that will remind you – such as next to your alarm, or with your coffee or tea.
  • Using a weekly pill box.
  • Marking the time on your calendar. 
  • Asking a family member or friend to remind you.
  • Always carrying a list of your medicines and their doses with you.
  • Entering a daily alarm in your mobile phone or download an app (such as NPS Medicinewise) to remind you.

Take any blood pressure medicine exactly as prescribed. Don’t stop or change your medicine, unless your doctor advises you to.

Where to get help

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Abstract

Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.

High blood pressure (BP) is a highly prevalent disorder, and its complications (including heart disease, stroke, and kidney disease) are a major public health problem (1). Despite decades of scrutiny, the precise pathogenesis of essential hypertension has been difficult to delineate. Guyton and his associates suggested that defective handling of sodium by the kidney and consequent dysregulation of body fluid volumes is a requisite, final common pathway in hypertension pathogenesis (2). The powerful capacity of this pathway to modulate blood pressure is illustrated by the elegant studies of Lifton and associates showing that virtually all of the Mendelian disorders with major impact on blood pressure homeostasis are caused by genetic variants affecting salt and water reabsorption by the distal nephron (3). On the other hand, several recent studies have suggested that primary vascular defects may cause hypertension by impacting peripheral resistance without direct involvement of renal excretory functions (4–7).

Among the various regulatory systems that impact blood pressure, the RAS has a key role. Inappropriate activation of the RAS, as in renal artery stenosis, leads to profound hypertension and cardiovascular morbidity (8). Moreover, in patients with essential hypertension who typically lack overt signs of RAS activation, ACE inhibitors and angiotensin receptor blockers (ARBs) effectively reduce blood pressure and ameliorate cardiovascular complications (9–11), suggesting that dysregulation of the RAS contributes to their elevated blood pressure.

At the cellular level, responsiveness to angiotensin II (Ang II) is conferred by the expression of the two classes of angiotensin receptors (AT1 and AT2). The effects of Ang II to increase blood pressure are mediated by AT1 receptors (12), and these receptors are expressed in a variety of organ systems thought to play key roles in blood pressure homeostasis, including the heart, kidney, blood vessels, adrenal glands, and cardiovascular control centers in the brain (13). For example, in the vascular system, stimulation of AT1 receptors causes potent vasoconstriction (14, 15). In the adrenal cortex, their activation stimulates the release of aldosterone (16) that in turn promotes sodium reabsorption in the mineralocorticoid-responsive segments of the distal nephron (17). In the brain, intraventricular injection of Ang II causes a dramatic pressor response that is mediated by AT1A receptors (18). In the kidney, activation of AT1 receptors is associated with renal vasoconstriction and antinatriuresis (19, 20). Nevertheless, whether angiotensin actions in these individual tissue sites contribute in vivo to the pathogenesis of hypertension and its complications is not clear.

To address this question, we used a kidney cross-transplantation strategy to separate the actions of AT1 receptor pools in the kidney from those in systemic tissues. Our findings suggest that AT1 receptors expressed in the kidney are the primary determinants of hypertension and end-organ damage in Ang II-dependent hypertension.

Results

Kidney Cross-Transplantation Model.

We used a kidney cross-transplantation strategy to separate the actions of AT1 receptor pools in the kidney from those in systemic tissues, as we have described previously (21). Kidney transplantation was carried out between genetically matched F1(C57BL/6 × 129) wild-type mice and F1(C57BL/6 × 129) mice homozygous for a targeted disruption of the Agtr1a gene locus encoding the AT1A receptor (14). The AT1A receptor is the major AT1 receptor isoform in the mouse and the closest mouse homologue to the human AT1 receptor gene (12).

By varying the genotype of the transplant donor and recipient, we generated four groups of animals in which renal function was provided entirely by the single transplanted kidney. The Wild-type group consisted of wild-type mice transplanted with kidneys from wild-type donors and thus have normal expression of AT1A receptors in the kidney transplant and in all systemic tissues. For the Systemic KO group, AT1A receptor-deficient recipients were transplanted with kidneys from wild-type donors; these animals lack AT1A receptors in all tissues except the kidney. Kidney KO animals are wild-type recipients of AT1A receptor-deficient kidneys, thus lacking expression of AT1A receptors only in the kidney, but with normal expression of receptors in all systemic, nonrenal tissues, including the adrenal gland. Finally, the Total KO group consists of AT1A receptor-deficient recipients of AT1A receptor-deficient kidneys and therefore completely lacking AT1A receptors in all tissues.

Baseline Blood Pressure Measurements.

One week after the transplantation procedure, radiotelemetry transmitters were implanted to provide direct measurements of arterial pressures in the mice in a conscious and unrestrained state. One week after placement of these units, when the animals had regained normal diurnal variation of blood pressure, blood pressure measurement was initiated. Baseline blood pressures in the Systemic KO and Kidney KO groups were virtually identical [109 ± 1 mmHg vs. 109 ± 1 mmHg (1 mmHg = 133 Pa)] and intermediate to those of the Wild-type (114 ± 2 mmHg) and Total KO (97 ± 2 mmHg) groups, consistent with our previous experiments (21) showing that renal and systemic AT1 receptors make equivalent contributions to the level of blood pressure in the basal state.

A Major Role for AT

1 Receptors in the Kidney in Ang II-Dependent Hypertension.

To distinguish the AT1 receptor population that is critical for the pathogenesis of hypertension, osmotic minipumps were implanted s.c. into each animal to infuse Ang II (1,000 ng/kg/min) continuously for 4 weeks. This is a widely used model of experimental hypertension in which elevated blood pressure is mediated by ligand stimulation of AT1 receptors causing significant end-organ damage, including cardiac hypertrophy (22–24). Upon initiation of Ang II infusion, mean arterial pressures (MAP) in the Wild-type transplant group rose dramatically to almost 160 mmHg (Fig. 1
A) and remained elevated throughout the infusion period (MAP of 166 ± 3 mmHg for Week 3 of infusion; mean BP increase of + 55 ± 3 mmHg). This degree of blood pressure increase is similar to that seen in previous studies using nontransplanted mice (23), suggesting that the transplant procedure and the presence of only a single kidney does not significantly alter blood pressure responses to chronic Ang II infusion. By contrast, blood pressures in the Total KO animals that are completely devoid of AT1A receptors were affected only minimally by Ang II infusion (Fig. 1
A), reflecting the key role of AT1 receptors in the development of hypertension in this model (MAP of 104 ± 3 mmHg at Week 3). The modest (+ 6 ± 3 mmHg; P = 0.05) increase in blood pressure in these animals was likely mediated by expression of the minor AT1 receptor isoform, AT1B, which is unaffected by the AT1A gene disruption (15).

Fig. 1.

Blood pressures and urinary sodium excretion in mice after kidney cross-transplantation. (A) Daily, 24-h blood pressures in the experimental groups before (“pre”) and during 21 days of Ang II infusion (∗, P ≤ 0.03 vs. Wild-type; §, P < 0.008 vs. Systemic KO; †, P < 0.006–0.0001 vs. Wild-type). (B) Cumulative sodium excretion during the first 5 days of Ang II infusion. (§, P < 0.02 vs. Kidney KO and P = 0.03 vs. Total KO; ‡, P = 0.03 vs. Kidney KO and Total KO). (C) Change in body weights after 5 days of Ang II infusion. (∗, P = 0.03 vs. “pre”; #, P = 0.05 vs. “pre”).

The Kidney KO animals (Fig. 1
A) experienced an immediate increase in blood pressure when the Ang II infusion was initiated, peaking on Day 2 (135 ± 5 mmHg; P < 0.0003 vs. Kidney KO baseline) and rapidly receding thereafter. However, at every time point, including Day 2, blood pressures in the Kidney KOs were significantly lower than those in the Wild-type group. Accordingly, the degree of hypertension was markedly attenuated in the Kidney KOs compared with the Wild-type group (MAP of 126 ± 5 vs. 166 ± 3 mmHg at Week 3; P = 0.0001). Moreover, the extent of the blood pressure increase in the Kidney KO group was not different from that seen in the Total KOs (+ 15 ± 4 mmHg; P = NS vs. Total KO). Despite the early and transient increase in blood pressure, presumably due to peripheral vasoconstriction, the absence of AT1A receptors in the kidney alone is sufficient to protect from Ang II-dependent hypertension.

In contrast, in the Systemic KO animals expressing AT1A receptors only in the kidney (Fig. 1
A), MAP rose progressively over the first 2 weeks of Ang II infusion. Yet, their blood pressures lagged behind the higher pressures seen in the Wild-type group for the first 10 days, likely reflecting the transient contribution of the early vasoconstrictor response seen in the Kidney KOs. Nonetheless, from Day 4 onward, blood pressures in Systemic KOs significantly exceeded those of the Kidney KOs (P < 0.008). Furthermore, by Day 12, blood pressures in the Systemic KOs converged with and were virtually identical to those of the Wild-type group (161 ± 5 mmHg for Week 3; mean BP increase of + 51 ± 4 mmHg; P = NS vs. Wild-type; P = 0.0003 vs. Kidney KO). Accordingly, the presence of AT1A receptors in the kidney alone is sufficient to recapitulate the hypertension phenotype of the Wild-type group. Together, these data show that Ang II causes hypertension primarily through AT1A receptors expressed in the kidney.

Urinary Sodium Excretion.

We reasoned that activation of AT1 receptors in the kidney might cause hypertension by influencing renal sodium handling (2). Therefore, we compared urinary sodium excretion between the experimental groups during the first week of Ang II infusion. The animals were placed in metabolic cages (25), and food and water intakes were matched to avoid confounding effects of variable intake on urinary electrolyte excretion. Before implantation of Ang II-infusion pumps, total urinary sodium excretion (UNaV) was similar in the four experimental groups (not shown). In contrast, cumulative sodium excretion measured during the first 5 days of Ang II infusion (Fig. 1
B) was significantly reduced in the hypertensive Wild-type and Systemic KO groups compared with the Kidney KO and Total KO groups. The latter two groups lack AT1A receptors in the kidney and are resistant to the hypertensive actions of Ang II (Fig. 1
A).

Impaired sodium excretion by the kidney may increase blood pressure by expanding intravascular fluid volume (2), which should be reflected acutely by changes in body weight. Therefore, to determine whether the reduced sodium excretion in the Wild-type and Systemic KO groups led to volume expansion, we compared body weights at baseline and after 5 days of Ang II infusion. Body weights increased significantly in the Wild-type (+ 5.9%) and Systemic KO (+ 4.2%) groups but did not change significantly in the Kidney KO and Total KO groups (Fig. 1
C), exactly paralleling the effects of Ang II on sodium excretion. These data indicate that Ang II causes hypertension by activating AT1 receptors in the kidney promoting sodium reabsorption. Conversely, when AT1 receptors in the kidney are absent, sufficient sodium is excreted in the urine to protect against the development of hypertension. These findings suggest that ACE inhibitors and ARBs reduce blood pressure in hypertensive patients by attenuating AT1 receptor signals in the kidney, thereby facilitating excretion of sodium.

Cardiac Hypertrophy Depends on Blood Pressure Elevation Rather Than Expression of AT

1 Receptors in the Heart.

In patients with hypertension, one of the early and most common consequences of chronic hypertension is left ventricular hypertrophy (LVH), and the presence of LVH is associated with significant cardiovascular risk (26, 27). Clinical evidence suggests that the RAS contributes to the development of LVH in hypertension (28–30). In our experiments, Systemic KO animals develop severe hypertension but lack AT1A receptors in the heart. Conversely, Kidney KO animals are resistant to Ang II-induced hypertension but have a full complement of cardiac AT1A receptors. Thus, we reasoned that we could use our model to separate the effects of elevated blood pressure from direct cellular actions of AT1 receptors in the development of cardiac hypertrophy.

Accordingly, we compared heart size in the four experimental groups. With Ang II infusion, the Wild-type group developed robust cardiac hypertrophy (Fig. 2
A, E, and I), the extent of which was similar to that of previous studies with intact Wild-type animals infused with Ang II (23). In the Systemic KO group, which develop hypertension but lack AT1A receptors in the heart, the degree of cardiac hypertrophy and increased left ventricular wall thickness was similar to that in the Wild-type group (Fig. 2
B, F, and I), indicating that cardiac AT1 receptors are not necessary for the development of hypertrophy in this model. In contrast, in the Kidney KO group, with the normal complement of cardiac AT1A receptors but without hypertension, there was no evidence of hypertrophy after Ang II infusion (Fig. 2
C, G, and I). Moreover, heart sizes and weights in the Kidney KO group were virtually identical to those of the Total KO group (Fig. 2
D, H, and I). These results suggest that prolonged stimulation of AT1 receptors in the heart, without blood pressure elevation, is not sufficient to cause cardiac hypertrophy in vivo. As shown in Fig. 3
J, there was a tight correlation between heart weight and blood pressure across all four experimental groups, suggesting that cardiac hypertrophy depends primarily on the level of blood pressure rather than the presence of AT1 receptors in the heart.

Fig. 2.

Cardiac hypertrophy with angiotensin II infusion. (AH) Representative hearts and left ventricular cross-sections after 28 days of Ang II infusion: A and E, Wild-type; B and F, Systemic KO; C and G, Kidney KO; D and H, Total KO. (I) Mean heart-to-body weight ratios after 28 days of Ang II infusion. The dashed line represents the mean heart-to-body weight ratio for noninfused Wild-type mice established in previous experiments in our laboratory (23). Wild-type and Systemic KO groups exhibit significant cardiac hypertrophy. (n ≥ 9 per group; §, P < 0.002 vs. Kidney KO and P = 0.0004 vs. Total KO; ‡, P = 0.003 vs. Kidney KO and P = 0.0008 vs. Total KO). (J) For the entire cohort, there was a significant positive correlation between heart-to-body weight ratio and blood pressure (R = 0.84. P < 0.0001).

Fig. 3.

Cardiac injury after angiotensin II infusion. (AD) Representative photomicrographs of heart sections stained with Masson trichrome. (Magnification: ×20.) Vascular lesions with perivascular infiltrates, medial expansion, and myocyte injury were common in hearts from the Wild-type (A) and Systemic KO (B) groups, whereas myocardial and vascular morphology were normal in the Kidney KO (C) and Total KO (D) groups. (E) Semiquantitative scoring of cardiac pathology (§, P < 0.002 vs. Kidney KO and P < 0.0003 vs. Total KO; ‡, P < 0.02 vs. Kidney KO and P < 0.004 vs. Total KO).

Cardiac Pathology with Ang II Hypertension.

We next examined the extent of cardiac histopathology in the four experimental groups. Sections from the Wild-type and Systemic KO groups showed significant and similar degrees of pathology (Fig. 3
A and B), including perivascular cellular infiltrates, vessel wall thickening, and myocardial injury. In contrast, vessel wall structure and myocardial architecture were normal in the Kidney KO sections (Fig. 3
C) and virtually indistinguishable from the Total KO hearts (Fig. 3
D). With quantitative scoring (Fig. 3
E), the two groups with hypertension (Wild-type and Systemic KO) displayed significant cardiac injury whether or not AT1A receptors were expressed in the heart, whereas cardiac injury was minimal in the Kidney KO group despite their normal expression of cardiac AT1A receptors.

Cardiac Gene Expression Patterns During Ang II Hypertension.

Although our evaluations of heart weight and histology indicate a dominant effect of blood pressure on cardiac pathology, we considered the possibility that these assessments might not be sufficiently sensitive to detect cellular actions of AT1 receptors in cardiac myocytes. During hypertrophic cardiac remodeling, gene expression in myocardium undergoes characteristic alterations, including enhanced expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), along with recapitulation of fetal gene expression patterns for myosin heavy chains (MHC) characterized by a down-regulation of α-MHC and up-regulation of the β-MHC isoform (31–34). Previous studies have suggested that Ang II may stimulate these processes (35, 36). We therefore examined cardiac mRNA expression for ANP, BNP, α-MHC, and β-MHC after 4 weeks of Ang II infusion. As shown in Fig. 4
A, levels of mRNA for both ANP and BNP were both dramatically increased in hearts from Wild-type animals compared with hearts from the Total KO group. Expression was similarly enhanced in the Systemic KO group despite their lack of cardiac AT1A receptors. In contrast, up-regulation of ANP or BNP mRNAs was not detected in the Kidney KO hearts despite their full complement of cardiac AT1A receptors. A similar pattern was observed in our measurements of β-MHC and α-MHC mRNA levels. As depicted in Fig. 4
B, the ratio of β-MHC/α-MHC expression was increased by nearly 4-fold in the Wild-type and Systemic KO groups compared with the Kidney KO and Total KO groups.

Fig. 4.

Cardiac gene expression in mice infused with angiotensin II. (A) Expression of ANP and BNP mRNA in hearts (n ≥ 8 per group; §, P = 0.003 vs. Kidney KO and P < 0.002 vs. Total KO; ‡, P = 0.004 vs. Kidney KO and P < 0.003 vs. Total KO; ∗, P = 0.02 vs. Kidney KO and P = 0.002 vs. Total KO; #, P = 0.01 vs. Kidney KO and P < 0. 002 vs. Total KO). (B) Ratio of cardiac β-MHC-to-α-MHC mRNA expression in hearts. (§, P = 0.01 vs. Kidney KO and P = 0.03 vs. Total KO; ‡, P = 0.002 vs. Kidney KO and P = 0.01 vs. Total KO).

Discussion

A major role for the RAS in promoting hypertension and its associated end-organ damage has long been recognized (37–39). These actions are mediated primarily by AT1 receptors (30, 40). Expression of AT1 receptors in key sites involved in regulation of peripheral vascular resistance, sodium balance, and activity of the sympathetic nervous system is also consistent with its critical role in blood pressure homeostasis. Because pharmacological antagonists and conventional gene knockouts produce global inhibition of AT1 receptors, it has been difficult to discriminate clearly which of these specific tissue sites mediate the pathogenic actions of AT1 receptors in hypertension. Accordingly, we developed an experimental model of kidney cross-transplantation in the mouse that allows for separation of AT1 receptor pools in the kidney from those in other tissues.

A major finding in our study is that AT1 receptors in the kidney are primarily responsible for the actions of Ang II to cause hypertension. This is clearly illustrated in the Systemic KO animals, where the presence of AT1A receptors only in the kidney is sufficient to recapitulate the phenotyope of hypertension with Ang II infusion. Conversely, in the Kidney KO group, the absence of AT1 receptors from the kidney alone is sufficient to protect these animals from Ang II-dependent hypertension, despite the expression of AT1A receptors in a number of other key areas that potentially impact blood pressure homeostasis, including the brain, the heart, the peripheral vasculature, and the adrenal gland. The mechanism for the distinct blood pressure responses in the two groups appears to be related to differences in renal sodium handling. Ang II infusion is associated with reduced renal sodium excretion and weight gain in the Systemic KO group, whereas the absence of renal AT1 receptors in the Kidney KOs is associated with enhanced natriuresis, no change in weight, and resistance to hypertension. It is important that these effects on blood pressure and sodium excretion are determined by direct actions of AT1 receptors within the kidney, independent of any contribution of Ang II-dependent aldosterone release.

Within the kidney, AT1 receptors are expressed on epithelial cells throughout the nephron, in the glomerulus, and on the renal vasculature (41, 42). In the proximal tubule, AT1 receptors promote sodium reabsorption by coordinately stimulating the sodium-proton antiporter on the luminal membrane along with the sodium-potassium ATPase on the basolateral surface (43, 44). AT1 receptors also affect sodium reabsorption in distal nephron segments, including the thick ascending limb, distal tubule, and collecting duct (45–48). In the collecting duct, for example, Bell and associates have shown that Ang II directly stimulates epithelial sodium channel activity through an AT1 receptor-dependent mechanism (49). AT1 receptors expressed in the renal vasculature also have important regulatory effects on sodium handling (50). Renal vasoconstriction caused by Ang II, which we have previously shown to be primarily mediated by AT1A receptors (51), reduces medullary blood flow, blunting the kidney’s excretory capacity for sodium (52, 53). Our study suggests that the primary mechanism of action of ACE inhibitors and ARBs to reduce blood pressure in hypertensive patients is attenuation of AT1 receptor signals at one or more of these key sites in the kidney.

In previous work focused on normal blood pressure homeostasis, we found that AT1 receptor actions in the kidney and extrarenal tissues made virtually equivalent contributions to preventing hypotension and supporting normal blood pressure (21). Thus, when circulatory volumes are threatened, the full range of AT1 receptor actions at key tissue sites is activated and apparently necessary to protect against circulatory collapse. On the other hand, their relative contributions appear to be quite different in hypertension where the population of AT1 receptors in the kidney assumes a preeminent role. In this regard, Guyton hypothesized that the substantial capacity for sodium excretion by the kidney provides a compensatory system of virtually infinite gain to oppose processes, including increases in peripheral vascular resistance, which would tend to increase blood pressure (2). It follows that defects in renal excretory function would be a prerequisite, therefore, for sustaining a chronic increase in intra-arterial pressure. Our current findings confirm the key role of altered renal sodium handling in Ang II-dependent hypertension and are completely consistent with Guyton’s hypothesis.

There was a statistically significant increase in blood pressure in the Kidney KO group coinciding with the initiation of the angiotensin II infusion. This increase in blood pressure rapidly peaked on Day 2 and then gradually returned toward baseline. We speculate that this early change in blood pressure was due to vasoconstriction mediated by AT1 receptors in the peripheral vasculature. Its rapid attenuation was likely due to the accompanying natriuresis. This pattern illustrates the relatively modest contribution of systemic vasoconstriction, in isolation, to the development of Ang II-dependent hypertension. Even at their peak, blood pressures in the Kidney KOs remained substantially lower than those in the Wild-type group. Furthermore, blood pressures in this group were consistently and substantially reduced compared with those of the Systemic KOs. Thus, chronic systemic vasoconstriction driven by Ang II has a very limited capacity to cause sustained hypertension.

The pattern in the Systemic KO group was quite different. Blood pressure increased progressively during the first 2 weeks, although the rate of rise was delayed compared with that of the Wild-type group. We suggest that this early difference reflects the absence of the transient vasoconstrictor response seen in the Kidney KOs. With time, however, pressures in the Systemic KOs eventually reach the level of the Wild-type group, indicating that AT1 receptor actions in the kidney are sufficient to generate the full hypertension phenotype. Moreover, as discussed below, the similar extent of cardiac hypertrophy seen in the Wild-type and Systemic KO groups, and its complete absence in the Kidney KO group, suggests that the late, sustained phase of hypertension provides the major stimulus for end-organ injury in this model.

A major goal of hypertension treatment is to prevent or ameliorate injury to key target organs, including the heart, kidney, and brain. One of the most prevalent manifestations of end-organ damage in hypertension is the development of LVH (26), and its presence confers substantial cardiovascular risk (26, 27). Although pressure load from elevated blood pressure clearly contributes to LVH, several lines of evidence suggest that activation of the RAS also plays a role. For example, Ang II, acting through AT1 receptors, stimulates hypertrophy of cardiac myocytes in culture (54, 55). In addition, clinical studies have demonstrated actions of ACE inhibitors and ARBs to cause regression of LVH more effectively than other classes of antihypertensive agents with similar levels of blood pressure control (28–30).

Although distinguishing the relative contributions of hypertension and cardiac AT1 receptor activation to the development of LVH in vivo has been difficult, we reasoned that our model might be useful for this purpose. The extent of blood pressure elevation was very similar in the Wild-type and Systemic KO groups, but they differ in their expression of AT1A receptors in the heart. Despite lacking cardiac AT1A receptors, the Systemic KO group developed robust LVH with heart weights that were not significantly different from those of the Wild-type group. By contrast, Kidney KOs with a normal complement of cardiac AT1A receptors do not develop significant hypertension and likewise have no appreciable change in their heart weights. Within the entire cohort, there was a tight linear correlation between heart weight and blood pressure irrespective of the presence or absence cardiac AT1A receptors. Thus, in a simple model of Ang II-dependent hypertension, the severity of cardiac hypertrophy was exclusively dependent on blood pressure. We found no evidence for a contribution of direct actions of AT1 receptors in the heart to promote LVH. Although our data are clear-cut, they do not necessarily obviate the results of well-designed prospective clinical trials demonstrating beneficial effects of ACE inhibitors or ARBs on regression of LVH (29, 30). Rather, they suggest that the benefits of these agents in LVH are not a consequence of blocking cellular actions of Ang II in the heart, but may be due to differences in the degree or pattern of blood pressure control that was achieved (56).

Direct effects of AT1 receptor activation to promote inflammation, fibrosis, and vascular damage have been implicated as pathways for facilitating end-organ damage in hypertension (22, 24, 57–61). In our studies, we found that Ang II infusion caused cardiac fibrosis and vascular pathology in the Wild-type and Systemic KO groups. On the other hand, hearts in the Kidney KOs appeared virtually normal, indicating that vascular injury and fibrosis in the heart were also consequences of elevated blood pressure rather than local actions of cardiac AT1 receptors. Cardiac hypertrophy is associated with characteristic alterations in gene expression, including up-regulation of ANP and BNP (31, 32), and recapitulation of fetal patterns for expression of myosin heavy chains (33, 34). It has been suggested that activation of AT1 receptors in cardiomyocytes may be sufficient to trigger this transcription profile (34, 35). However, as we observed with cardiac hypertrophy and pathology, activation of AT1 receptors in the heart is not responsible for characteristic gene expression patterns associated with Ang II infusion; these are also triggered by elevated blood pressure.

In summary, these studies provide incontrovertible evidence that angiotensin II causes hypertension through actions of AT1 receptors expressed in the kidney that reduce urinary sodium excretion. This is a direct effect of AT1 receptors in the kidney that does not involve or require angiotensin II-mediated aldosterone responses in the adrenal gland. Our findings suggest that the mechanism of antihypertensive actions of ACE inhibitors and ARBs involves attenuation of the renal actions of angiotensin II. Furthermore, these experiments indicate that the major mechanism of protection from cardiac hypertrophy afforded by these agents is related to blood pressure control rather than inhibition of AT1 receptor actions in the heart.

Materials and Methods

Animals.

(129 × C57BL/6)F1 mice lacking AT1A receptors for Ang II were generated as described in ref. 14. Animals were bred and maintained in the animal facility of the Durham Veterans Affairs Medical Center under National Institutes of Health guidelines. These studies used 2- to 4-month-old male mice.

Mouse Kidney Transplantation.

Vascularized kidney transplants were performed in mice as described in ref. 21. The donor kidney, ureter, and bladder were harvested en bloc, including the renal artery with a small aortic cuff and the renal vein with a small vena caval cuff. These vascular cuffs were anastomosed to the recipient abdominal aorta and vena cava, respectively, below the level of the native renal vessels. Donor and recipient bladders were attached dome to dome. The right native kidney was removed at the time of transplant, and the left native kidney was removed through a flank incision 1–3 days later. The adrenal glands and their blood supply were preserved intact. Each group consisted of at least seven animals.

Telemetry Probe Implantation Procedure.

The components of the radiotelemetry system (Transoma Medical, St. Paul, MN), including the mouse blood pressure telemetry device (TA11PA-C20), are described in ref. 62. Six to 8 days after the kidney transplantation procedure, the pressure catheter was implanted in the left carotid artery as described in ref. 63.

Telemetric Blood Pressure Analysis.

Data were collected, stored, and analyzed by using Dataquest A.R.T. software (Transoma Medical). Blood pressures were measured on unanesthetized, unrestrained animals beginning 7 days after the catheter implantation when the mice had reestablished normal circadian rhythms (63). Telemetry data were collected continuously with sampling every 6 min for 10-s intervals (62).

Experimental Protocol.

Baseline blood pressure measurements were determined on 3 consecutive days while the animals ingested a normal diet containing 0.4% sodium chloride. After these baseline recordings, an osmotic minipump (Alzet Model 2004; DURECT) infusing Ang II (Sigma, St. Louis, MO) at a rate of 1,000 ng/kg/min was implanted s.c. as described in ref. 23, and blood pressure measurements continued for 21 days.

Metabolic Balance Studies.

One week after transplantation, the animals were placed in specially designed metabolic cages (23). The mice were fed 10 gm/day gelled 0.25% NaCl diet that contained all nutrients and water (Nutra-gel; Bio-Serv, Frenchtown, NJ). After 1 week of baseline collections, the animals were implanted with osmotic minipumps infusing Ang II as described above and were returned to the metabolic cage for 5 more days. Urinary sodium content was determined by using an IL943 Automatic Flame photometer per the manufacturer’s instructions (Instrumentation Laboratory, Lexington, MA).

Histopathologic Analysis.

After 28 days of Ang II infusion, hearts were harvested, weighed, fixed in formalin, sectioned, and stained with Masson trichrome. All of the tissues were examined by a pathologist (P.R.) without knowledge of genotypes. Pathology was graded based on the presence and severity of component abnormalities, including cellular infiltrate, myocardial cell injury, vessel wall thickening, and fibrosis. Grading for each component was performed by using a semiquantitative scale where 0 was normal and 1–4+ represented mild through severe abnormalities. The total cardiac injury score for each heart was a summation of the component injury scores.

Quantification of Cardiac mRNA Expression.

Hearts were harvested, and total RNA was isolated by using an RNeasy mini kit per the manufacturer’s instructions (Qiagen, Valencia, CA). The gene expression levels of ANP, BNP, α-MHC, and β-MHC in cardiac tissue were determined by real-time quantitative RT-PCR as reported in ref. 64.

Statistical Analysis.

The values for each parameter within a group are expressed as the mean ± SEM. For comparisons between groups with normally distributed data, statistical significance was assessed by using ANOVA followed by an unpaired t test; within groups, a paired t test was used. For nonparametric comparisons, the Mann–Whitney U test was used between groups, and the Wilcoxon signed rank test was used within groups.

Acknowledgments

We acknowledge outstanding administrative support from Ms. Norma Barrow and technical support from Mr. Chris Best. This work was supported by National Institutes of Health Grants HL49277 and HL56122 and by funding from the Medical Research Service of the Department of Veterans Affairs.

Footnotes

  • §To whom correspondence should be addressed at:

    Duke University Medical Center, Box 3014, Durham, NC 27710.

    E-mail:
    tcoffman{at}duke.edu

  • Author contributions: S. D.C., O.S., T.H.L., and T.M.C. designed research; S.D.C., S.B.G., M.J.H., P.R., R.G., A.P.K., and H.-S.K. performed research; S.D.C., S.B.G., P.R., T.H.L., and T.M.C. analyzed data; and S.D.C., O.S., T.H.L., and T.M.C. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS direct submission.

  • © 2006 by The National Academy of Sciences of the USA

Resting heart rate | healthdirect

beginning of content

2-minute read

Your resting heart rate, or pulse, is the number of times your heart beats per minute when you are at rest – such as when you are relaxed, sitting or lying down.

Resting heart rate varies from person to person. Knowing yours can give you an important sign of your heart health.

What is a normal resting heart rate?

For adults, a normal resting heart rate ranges between 60 and 100 beats a minute.

Usually, a lower resting heart rate means your heart is working more efficiently and is more fit.

For example, an athlete might have a resting heart rate of around 40 beats a minute.

How do I check my resting heart rate?

To check your heart rate:

  • Sit down and rest for 5 minutes.
  • Turn your wrist so your palm is facing up.
  • Feel for a pulse at thumb side of your wrist.
  • Once you feel it, count how many times you feel a beat in 30 seconds. Then double it.

If you can’t find your pulse at your wrist, put 2 fingers on the side of your neck, next to the windpipe.

If you still can’t find a pulse, ask someone else to feel it for you.

Which factors can influence heart rate?

Many things can affect your heart rate, including:

  • physical activity — if you’ve been moving around a lot, your heart rate will increase
  • fitness level — your resting heart rate may be lower if you’re very fit
  • air temperature — on hot days, your heart needs to pump more quickly
  • emotions — such as feeling stressed or overly excited
  • medicines — some can decrease your resting heart rate (e. g. beta blockers), while others can increase it (e.g. thyroid medicines)
  • age — with age, the rate and regularity of your pulse can change and can be a sign of a heart problem.

If my resting heart rate is normal, is my blood pressure normal?

Your resting heart rate is not an indication of your blood pressure. The only way to check blood pressure is to measure it directly.

If my resting heart rate is slow, is it dangerous?

People can have a resting heart rate of 40 if they are very fit. But a slow pulse could also be a sign of problems. If you are not sure, or if you have been feeling faint, dizzy or short of breath, see your doctor.

If my resting heart rate is fast, is it dangerous?

A fast resting heart rate (higher than 100 beats per minute) can be a sign of problems. See your doctor for advice.

Learn more here about the development and quality assurance of healthdirect content.

Last reviewed: March 2020

What your heart rate is telling you

Your pulse, both at rest and during exercise, can reveal your risk for heart attack and your aerobic capacity.

Your grandmother may have referred to your heart as “your ticker,” but that nickname has proved to be a misnomer. A healthy heart doesn’t beat with the regularity of clockwork. It speeds up and slows down to accommodate your changing need for oxygen as your activities vary throughout the day. What is a “normal” heart rate varies from person to person. However, an unusually high resting heart rate or low maximum heart rate may signify an increased risk of heart attack and death.

One simple thing people can do is to check their resting heart rate. It’s a fairly easy to do and having the information can help down the road. It’s a good idea to take your pulse occasionally to get a sense of what’s normal for you and to identify unusual changes in rate or regularity that may warrant medical attention.

Your resting heart rate

When you are at rest, your heart is pumping the lowest amount of blood to supply the oxygen your body’s needs. For most healthy adult women and men, resting heart rates range from 60 to 100 beats per minute. However, a 2010 report from the Women’s Health Initiative (WHI) indicated that a resting heart rate at the low end of that spectrum may offer some protection against heart attacks. When WHI researchers examined data on 129,135 postmenopausal women, they found that those with the highest resting heart rates—more than 76 beats per minute—were 26% more likely to have a heart attack or die from one than those with the lowest resting heart rates—62 beats per minute or less. If your resting heart rate is consistently above 80 beats per minute, you might want to talk to your doctor about how your heart rate and other personal factors influence your risk for cardiovascular disease.

Your maximum heart rate

The rate at which your heart is beating when it is working its hardest to meet your body’s oxygen needs is your maximum heart rate. Your maximum heart rate plays a major role in setting your aerobic capacity—the amount of oxygen you are able to consume. Several large observational studies have indicated that a high aerobic capacity is associated with a lower risk of heart attack and death. And a small controlled trial demonstrated that men and women with mild cognitive impairment who raised their aerobic capacity also improved their performance on tests of memory and reasoning.

The role of exercise

Vigorous exercise is the best way to both lower your resting heart rate and increase your maximum heart rate and aerobic capacity. Because it’s impossible to maintain a maximum heart rate for more than a few minutes, physiologists have advised setting a percentage of your maximum heart rate as a target during exercise. If you’re starting an exercise program, you may want to set your target rate at 50% of maximum and gradually increase the intensity of your workout until you reach 70% to 80%.

However, if you don’t exercise regularly, you should check with your doctor before you set a target heart rate. Some medications—particularly beta blockers—can lower your heart rate. Your doctor can help you set realistic goals.

How to take your pulse

Although you may be able to feel your blood pumping in a number of places—your neck, the inside of your elbow, and even the top of your foot—your wrist is probably the most convenient and reliable place to get a good pulse.

Press your index and middle fingers together on your wrist, below the fat pad of your thumb. Feel around lightly until you detect throbbing. If you press too hard you may suppress the pulse. You can probably get a pretty accurate reading by counting the number of beats in 15 seconds and multiplying that number by four.

The best time to get your resting heart rate is first thing in the morning, even before you get out of bed. To gauge your maximum heart rate, take your pulse immediately after exercising as vigorously as possible.

Image: Peera_Sathawirawong/Getty Images

 

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90,000 What is normal blood pressure at what age?

Blood pressure is a purely individual indicator and depends on many factors. And, nevertheless, there is a certain average medical norm. That is why deviations from the accepted indicators allow the doctor to suspect malfunctions in the body’s systems. However, the indicators change depending on the time of day and on the age of the person.

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Normal pressure in an adult should be determined only at rest, since any stress (both physical and emotional) has a huge impact on his performance. The human body independently controls blood pressure, and with a moderate load, its indicators rise by about 20 mm Hg. This is due to the fact that the muscles and organs involved in the work require a better blood supply.

According to the “Newest Reference Book of Necessary Knowledge”, normal blood pressure in newborns is 70 mm Hg. Normal blood pressure in a child who is one year old: boys – 96/66 (upper / lower), girls – 95/65. Reported by poradamamu.in.ua

Normal blood pressure in a 10-year-old child: 103/69 in boys and 103/70 in girls.

Normal blood pressure in young people 20 years old: in boys – 123/76, in girls – 116/72.

Normal blood pressure for those who are about 30 years old: for men – 126/79, for young women – 120/75.

In a middle-aged person: in 40-year-old men 129/81, in 40-year-old women 127/80.

For fifty-year-old men and women: Pressure is considered normal for men 135/83 and for women 137/84.

For elderly people:
The following pressure is considered normal: for 60-year-old men 142/85, for women of the same age 144/85.

For seniors who have turned 70 years old: normal pressure is 145/82 for men and 159/85 for women. What is the normal blood pressure of an old or elderly person? For 80-year-old people, pressure 147/82 and 157/83 for men and women, respectively, is considered normal. For elderly ninety-year-old grandfathers, the normal pressure is 145/78, and for grandmothers of the same age – 150/79 mm. rt. pillar. Blood pressure consists of two numbers, the upper number is the renal pressure, the lower number is the heart pressure.

How to measure pressure?

There is a special device for measuring blood pressure – a tonometer. At home, it is most convenient to use an automatic or semi-automatic device.

To obtain correct results, the following recommendations must be observed:

  • Before measuring pressure, physical activity must be completely eliminated;
  • No smoking;
  • measuring blood pressure immediately after eating will also give incorrect results;
  • measure blood pressure while sitting in a comfortable chair;
  • the back must be supported;
  • The hand on which the measurement is taken must be located at the level of the heart, i. e.e. pressure is measured while sitting at the table;
  • when measuring pressure, you need to remain motionless and not talk;
  • readings are taken from both hands (measuring interval 10 minutes)

What to do if the pressure is high (help):

1. Pour hot water with a temperature of 37-40 ° C into a basin or a bucket and immerse your feet in the water. While the water cools down – it will take about 20 minutes – the pressure will drop by 15-20 mm. If a person has varicose veins on the legs, you can lower your elbows into the water.

2. Dill seeds reduce blood pressure. You need to steam them with boiling water, taking 2 tbsp. spoons for 0.5 liters of boiling water, drink 1-2 teaspoons at a pressure of up to 200 mm and 3-4 tsp. at higher pressure.

3. Add 1 tsp to kefir. cinnamon, drink this drink in 1 glass for 3 months. The pressure should stabilize. There is one very simple and incredibly effective recipe for traditional medicine that will help bring blood pressure back to normal, well, at least for a couple of years. And besides, it doesn’t cost a dime. So the composition of the broth: take 5 tablespoons of pine needles, 2 tablespoons of rose hips and 2 tablespoons of onion husks. Pour all this with 1 liter of cold water, bring to a boil and cook over low heat, covered for 10 minutes. Let it brew and strain. You can add a little water. Drink it all in 2 days. The course of such treatment is 4 months. Improvement can come within 5 days – the headaches will go away, and after a month you can try to gradually cancel antihypertensive drugs.The stool will become regular, which means that the intestines and liver are also cleansed. This broth has immuno-strengthening properties, is a prophylactic agent against influenza. It has a good diuretic effect. It will help with painful bleeding of the gums.

90,000 Hypotension during pregnancy – 9,0001

In many women, blood pressure decreases slightly during pregnancy, this does not significantly affect the general well-being, but with a sharp and strong decrease it can be dangerous.

If a woman had hypotension before pregnancy, then during pregnancy she should pay special attention to pressure. With hypotension, it is not always low, for example, after rest, in the first half of the day it may be normal. The pressure can rise sharply with excitement, and then quickly decrease. It is believed that hypotension occurs with hormonal deficiency.

In early pregnancy, hypotension can aggravate early toxicosis, while if a pregnant woman has frequent vomiting, dehydration may occur, which aggravates the disease, so a woman is better off in the hospital during this period, since it is necessary to inject liquid by drip.The danger of hypotension for pregnant women is that low pressure leads to a reduction in blood flow in the placenta, uterus and fetus, so-called fetal malnutrition can occur.

The unborn child suffers from nutritional deficiencies and oxygen deficiency, which leads to a slowdown in its growth, and, even worse, can lead to a miscarriage. Although in most cases the disease does not cause big problems on the part of the fetus, the pregnant woman herself has a hard time. With hypotension, the state of health may change several times a day, dizziness will appear, the pregnant woman gets tired quickly, sweats a lot, and even fainting, heart palpitations and pain in the heart may occur.

This condition can occur from hunger, after taking a hot bath or lack of oxygen in a stuffy room. Changes in the emotional state are often associated with this disease, when the mood changes very quickly and for no reason, although this is typical for all pregnant women, but in patients with hypotension, it manifests itself more clearly. This state should be avoided whenever possible. In late pregnancy, women suffering from hypotension may experience preeclampsia. This is often caused by weakened pressure control, because low blood pressure is less often noticed than high blood pressure.

Hypotension is not a reason to terminate a pregnancy. Although with this disease, women are five times more likely to develop toxicosis than healthy ones. There is a relationship between hypotension and spontaneous abortion. Also, low blood pressure can affect the normal course of labor, due to poor blood supply to the uterus, therefore, cesarean section for patients with hypotension is done more often.

Pregnant women with hypotension should be examined regularly. Good rest is very important for hypotensive patients; sleep should be prolonged for about ten hours.Try to avoid overwork, walking in the fresh air is mandatory. Meals should be sufficiently high in calories, with a full-fledged protein content, only you should refrain from overeating, eat 5-6 times during the day, try not to allow long breaks between meals, with a hungry state, hypotensive patients often have low sugar.

Products containing vitamins B and C must be present. Tea and coffee can be drunk, but not at night. Aromatic baths, warm, not hot, and a contrast shower will be of great benefit to those suffering from hypotension. Medicines or herbal treatments should be supervised by a physician. If you follow all the rules, then pregnancy with this disease ends safely.

RATIONALE

ometendo Obesity and Metabolism 2071-87132306-5524Endocrinology Research Center10.14341 / omet2018130-38Research Article Eating behavior and appetite-regulating hormones in patients with type 2 diabetes mellitus and a body mass index mailing over 35 kg / m2ruTsoiUlyana [email protected] [email protected] [email protected] V.A. Almazov ” Ministry of Health of Russia

Federal State Budgetary Institution North-West Federal Medical Research Center named after V. V.A. Almazov ” Ministry of Health of Russia

Federal State Budgetary Institution North-West Federal Medical Research Center named after V.V.A. Almazov ” Ministry of Health of Russia

Federal State Budgetary Institution North-West Federal Medical Research Center named after V. V.A. Almazov ” Ministry of Health of Russia

250420181513038

Rationale. The role of eating hormones in appetite regulation is well understood, but their relationship with different types of eating behavior has not been established.

Target. To study the frequency of different types of eating behavior, the feeling of hunger / satiety on a visual analogue scale, and the level of leptin and gastrointestinal hormones (ghrelin and glucagon-like peptide-1) involved in the regulation of appetite, fat and carbohydrate metabolism in patients with type 2 diabetes and obesity.

Materials and methods. The study included 35 obese people (BMI> 35 kg / m2) and type 2 diabetes mellitus (T2DM), median body mass index (BMI) 40.1 [36.5; 49.6] kg / m2, age 58 [52.5; 64] years, on stable therapy. All patients were tested for insulin, HOMA-IR and HOMA-β, leptin, ghrelin, glucagon-like peptide-1, C-peptide, glucose, glycated hemoglobin and lipids. All patients completed questionnaires characterizing eating behavior and the severity of hunger / satiety.

Results. In patients with T2DM and obesity, a high frequency of a combination of various types of eating behavior was revealed (54.3%); in an isolated form, a restrictive type of eating behavior was most often encountered (40%). A tendency to differences in the level of hormones regulating appetite, which did not achieve significant differences, was revealed in patients with different types of eating behavior. There was a high frequency of adequate decrease in the level of ghrelin after meals in patients with restrictive eating behavior.The relationship between the level of hormones regulating appetite and hunger and satiety was rather weak, which may be a manifestation of resistance to them in patients with severe obesity and type 2 diabetes mellitus. At the same time, the relationship between the level of ghrelin and the parameters characterizing the functional state of β-cells turned out to be significant.

Conclusion. The severity of resistance to leptin and ghrelin correlates with each other in patients with T2DM and obesity; the severity of resistance to ghrelin is associated with the functional state of beta cells; The post-food level of ghrelin can have multidirectional changes in patients with type 2 diabetes and obesity, and its adequate decrease is more typical for patients with a restrictive type of eating behavior.

obesity type 2 diabetes mellitus eating behavior grelinlepinglucagon-like peptide-1 BACKGROUND

Dysregulation in the eating behavior system (FS) is currently considered one of the leading causes of the obesity epidemic.

According to the Dutch Eating Behavior Questionnaire (DEBQ), 3 types of PP disorders can be distinguished, characterized by the following features:

Eating behavior is controlled by a complex system that includes central and humoral regulation links [1].The cortex and reward zones in the limbic system (“hedonic” regulation) play a key role in providing central mechanisms, in which stimuli from the environment are analyzed, both food (appearance, taste, smell of food) and nonfood (emotional discomfort, stress) [2], and the hypothalamus, the stimulation of the ventromedial nuclei of which is accompanied by a decrease in appetite, and the stimulation of the lateral nuclei is accompanied by an increase [3]. The leading role in providing humoral (homeostatic, peripheral) regulation is played by the hormones of the gastrointestinal tract (GIT) and adipose tissue (VT) [4]. More than 20 hormones are known that are involved to varying degrees in the regulation of PP and have orexigenic or anorexigenic effects [4, 5]. Among the hormones with orexigenic action, ghrelin plays the leading role, and the most important anorexigenic hormones are the gastrointestinal hormone glucagon-like peptide-1 (GLP-1) and the VT hormone leptin. There is no doubt that the impairment of the effects of these hormones plays an important role in dysregulation of the PN system and in the development of hyperphagia, which is characteristic of obese patients [4]. To date, data have been obtained confirming the role of these hormones in the interaction between the homeostatic and hedonic pathways of appetite regulation.It has been shown that leptin affects the sense of taste and the limbic reward system [7], while ghrelin stimulates the mesolimbic dopaminergic pathway and increases the consumption of sugary foods [7, 8].

Ghrelin is a neuroendocrine hormone of the gastrointestinal tract (mainly the fundus of the stomach) [7, 8], which stimulates the secretion of growth hormone [7], hungry gastric motility, appetite and provides a positive energy balance, which is accompanied by weight gain [8]. Ghrelin, acting as a leptin antagonist, regulates the synthesis and secretion of hypothalamic neuropeptides that regulate hunger and satiety centers (neuropeptide Y (NPY) and agouti-linked peptide (AgRP)), stimulating hunger [7].In healthy people without obesity, the level of ghrelin is maximally increased on an empty stomach (approximately two times), can remain elevated in the first 20 minutes after the start of a meal, and decreases in the post-meal period by 35–55%, reaching a maximum decrease in about an hour after the start of a meal and maintaining this maximum decrease within 150–250 minutes [8]. The decrease in the level of ghrelin after a meal depends on its calorie content and composition: its decrease is more significant after a fatty meal in comparison with a carbohydrate or protein-containing one.Dietary fiber content also affects the post-nutritional dynamics of ghrelin levels [9]. This fact requires standardization of nutrition when studying the level of ghrelin in various clinical situations. In addition, ambient temperature and sleep duration affect ghrelin production. Fasting ghrelin levels are significantly reduced in most obese patients and are negatively correlated with BMI, body fat (% body fat), and fasting insulin and leptin levels [8, 10]. Meanwhile, in various works there are conflicting data on the dynamics of the post-nutritional level of ghrelin in obese people.Adamska E. et al. [5] noted a more pronounced decrease in the level of ghrelin after meals in obese people. However, most studies have noted an insufficient decrease in plasma ghrelin after meals or its absence in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (DM2) [10, 11], which may contribute to increased food intake due to the lack of timely appearance of feeling saturation and formation of pathological PP. It cannot be ruled out that in patients with different types of PP impairment, changes in the level of ghrelin after meals may be of a different nature.T2DM is a disease also associated with increased appetite. In the pathogenesis of diabetic hyperphagia, the role of hyperinsulinemia, GLP-1 deficiency and changes in the level of ghrelin and leptin is discussed [12]. In experimental models of diabetes, an increase in the level of ghrelin and a decrease in leptin were noted [7], however, when examining patients with diabetes without significant obesity, the level of ghrelin did not differ significantly from healthy controls [8], and in patients with IR and obesity it was reduced [10]. The study of changes in the level of ghrelin in diabetes is significantly complicated by the fact that the level of ghrelin is interrelated with the level of glucose and insulin [8, 10], which means that its level may be influenced by the degree of compensation for diabetes, the nature of therapy, the severity of IR and / or insulin deficiency.

GLP-1 – incretin produced mainly by L-cells of the gastrointestinal tract and, to a lesser extent, by neurons of the central nervous system. Under the influence of GLP-1, appetite decreases, food evacuation from the stomach slows down, the production of hydrochloric acid and glucagon is inhibited, which accelerates the onset of satiety, and insulin production increases in a glucose-dependent way [6, 13]. Receptors for GLP-1 are expressed in the central nervous system, hypothalamus, peripheral nerve fibers, and the gastrointestinal tract (pancreas) [13]. GLP-1 inhibits the production of orexigenic hypothalamic neuropeptides NPY and AgRP and increases the expression of the proopiomelanocortin (POMK) gene and its secretion [13], accelerating the onset of satiety.The contribution of GLP-1 to the regulation of PP is complex, and its effects on appetite are mediated in three ways: GLP-1 from the gastrointestinal tract acts endocrine and through the afferent fibers of the vagus nerve. GLP-1, produced in the central nervous system, acts in a non-receptor way, penetrating the blood-brain barrier and affecting the nuclei of tractus solitarius, the postrema region, and the motor nucleus of the vagus [6, 13]. In healthy people, GLP-1 levels are very low on an empty stomach and rise rapidly after carbohydrate and fat-containing foods [4]. In patients with both obesity and T2DM, the level of GLP-1 is usually reduced [6, 13], and in patients with high degrees of obesity, not only the basal level of GLP-1 is sharply reduced, but also its postprandial increase is practically absent [ 4]. In most patients with T2DM, not only the production of GLP-1 is reduced, but also the sensitivity to its physiological levels [14].

Leptin is a hormone that is produced mainly in adipose tissue and in small amounts in the gastric fundus mucosa, skeletal muscles, and mammary epithelium [4]. Leptin provides afferent signaling to the central nervous system (CNS) about the number of VT, inhibits the activity of neuropeptide-Y-containing neurons (hunger center) and stimulates POMC-containing neurons (saturation center).The specific transport system of leptin allows it to penetrate the blood-brain barrier, exerting effects in the central nervous system [6]. An increase in the level of leptin not only ensures the onset of a feeling of satiety during meals, increases thermogenesis and the rate of metabolic processes, but also inhibits gluconeogenesis in the liver, reduces the utilization of glucose by tissues, causing insulin resistance of skeletal muscles and VT. Thus, it is involved in the regulation of not only adipostat, but also carbohydrate metabolism. Leptin increases the expression of GLP-1 receptors in the hypothalamus, increasing sensitivity to it and its production in the central nervous system [6].In obese individuals, as a rule, the level of leptin in the blood is high, which is explained by the resistance to this hormone [4]. The dynamics of the level of leptin in obesity is sex-dependent, and the level of plasma leptin increases in obese women much more than in men [4].

So, the assessment of hormones that regulate appetite is complicated, firstly, by the fact that their level is influenced by a number of factors (sleep duration, ambient temperature, stress, gender and sex hormone levels, the post-food level is influenced by the amount and nature of food ).Second, obese patients may develop resistance to them. The literature contains data on the development of resistance to both GLP-1 [13] and leptin [4], and to ghrelin [10], correlating with BMI. Therefore, when studying their contribution to PP, it is necessary to assess not only the fasting level of these hormones, primarily ghrelin, but also changes in their level in response to food intake.

With obesity, pronounced changes develop in both the hormonal and psychoemotional spheres, which have a pronounced effect on the formation of pathological PN [1].Violation of PP can occur under the influence of various factors (genetic disorders, pathology of the central nervous system, psychological characteristics of the patient’s personality, social factors, stress), including the imbalance of hormones that regulate appetite. It is highly likely that the levels of these hormones in obese patients may differ in different types of PN disorders.

In the case of an external type of eating behavior (ETPP), various external stimuli (advertising food, the type of table set) can become leading to start eating due to impaired sensitivity to hormones of appetite [1].In the emotiogenic type of PP disorder, the stimulus for food intake is stress, and, probably, stress hormones play a significant role in it. Glucocorticoids (GC) regulate the activity of leptin, increasing its production, but at the same time reducing sensitivity to it and reducing its effects [4].

Insulin is also an appetite-regulating hormone, manifesting its activity in the hypothalamus in the ventral tegmental zone, where it reduces food intake and pleasure from food mediated through dopaminergic neurons [4, 14].HA sharply increase insulin production, but with a chronic excess of HA, IR develops [15]. HA reduces the ability of insulin and leptin to inhibit NPY / AGRP neurons and suppress appetite [15]. Ghrelin production increases in response to stress [15], and chronic stress significantly increases ghrelin-mediated NPY / AGRP activity, hunger, and food intake [15]. Eating food, especially sweet food, reduces the activity of the ACTH-adrenal axis, arresting GC-mediated manifestations of stress and consolidating the emotiogenic type of PP disorder.

Few attempts to assess the relationship of hormones regulating appetite with types of eating behavior have been made earlier [16], but there is no clear idea of ​​how their level changes with various disorders of PP. We also did not find any studies in the available literature that investigated the relationship between post-nutritional ghrelin level and the type of PP disorder in patients with T2DM and obesity. The influence on the type of PP disorder of the nature of T2DM therapy (therapy that increases insulin levels, or therapy that increases insulin sensitivity), the characteristics of the course of diabetes (the severity of IR and the preservation of the reserve function of β-cells) remains poorly understood.

PURPOSE

Thus, the aim of this study was to study the relationship between the type of PP disorder and the level of hormones that regulate appetite and the characteristics of the course of the disease and treatment in patients with type 2 diabetes and obesity (BMI ≥35 kg / m2).

METHODS

Study design – open, one-stage, transverse

When included in the study, the following were carried out:

The study was approved by the ethics committee of the VA Almazov “of the Ministry of Health of the Russian Federation (protocol No. 63 of 04/14/2014).

Examination of the patients included in the study consisted of a survey (complaints, medical history), physical examination with measurement of anthropometric (age, sex, height, body weight, waist circumference (WC), calculation of BMI) and clinical (BP, heart rate, RR) parameters, assessment of the levels of C-peptide, insulin, ghrelin, GLP-1 and leptin on an empty stomach and ghrelin and C-peptide after a standard breakfast, with the calculation of indicators reflecting the severity of IR and the state of reserve function of beta cells, filling out questionnaires.To assess IR, the HOMA-IR index (Homeostasis Model Assessment) = I0xG0 / 22.5 (norm <2.77) and an additional IR marker proposed by ATP III: the ratio of TG / HDL cholesterol (norm <1.32) were used. To assess the activity of β-cells, the HOMA-β index = 20xI0 / (G0-3.5) was used - the norm is <180% and the degree of increase in the level of C-peptide after a standard carbohydrate breakfast (norm> 50%, or> 9.9 ng / ml).

The study used the European Food Propensity Questionnaire, the Dutch Eating Behavior Questionnaire (DEBQ), the visual analogue scale for recording appetite sensations VAS – Fasting state.The hormone levels were assessed by the enzyme immunoassay: ghrelin – on the RayBioTech test system (USA), insulin, GLP-1 and leptin – on the ARCHITECT I 1000SR analyzer from Abbott (USA), C-peptide – on the Elycsys 2010 analyzer (Table 1) … For the sample with a standard breakfast, a nutrient solution was prepared using 190 ml of pure water and 80 g of Clinutren Optimum enteral nutrition mixture, and the baseline levels of ghrelin and C-peptide were determined and their levels were determined 2 hours after consumption of the formula.

Table 1.Laboratory reference values ​​

/ ml

90 130

L 1 ,> 1.2 for women

Indicator Measurement units Reference intervals
Glycated hemoglobin % <6% 30 ​​ppm , 0
C-peptide ng / ml 0.78-1.89
Ghrelin pg / ml 8.502-16.6
GLP-1 ng / ml 0.2-10
Leptin ng / ml Women 1.1-27.6 ng / ml,
men 0.5-13.8 ng / ml
Glucose mmol / L 3.3-6.1
Total cholesterol mmol / L 3.5-4.5
LDL cholesterol mmol / L less than 1.8
Triglycerides mmol / L less than 1.7
Cholesterol

mmol / L

Notes: GLP-1 – glucagon-like peptide 1, LDL – low density lipoproteins, HDL – high density lipoproteins

The reference intervals for the main studied parameters are presented in Table 1.

Statistical processing of research results

Statistical analysis was carried out using the IBM SPSS Statistics 23 software and Statistica v.7.0 software. Descriptive characteristics are presented as median and quartiles (25th and 75th percentiles). To assess the differences between dependent samples, the nonparametric Wilcoxon test was used. The Mann-Whitney rank test was used to assess the significance of differences in independent variables. The analysis of the relationship (correlation) of two quantitative features was carried out according to Spearman.Comparisons between the different groups were performed using one-way analysis of variance (ANOVA) using the a posteriori Student-Newman-Keles test. Chi-square (Fisher’s exact test) was used to compare nominal variables. Differences were considered significant at p <0.05.

RESULTS

The study included 35 patients with type 2 diabetes and obesity (BMI ≥35 kg / m2) and meeting the following criteria.

Criteria for exclusion from the study.

Patient characteristics are presented in Table 2. Based on the results of the questionnaires, the type of PN and the severity of hunger / satiety in the morning on an empty stomach were determined.

Table 2. Characteristics of patients included in the study

Parameter Patients, n = 35
Age, years (Me [25; 75]) 58 [52.5; 64]
Duration of diabetes mellitus 10 [5.55; 19.9]
Body mass, kg (Me [25; 75]) 112 [107; 137]
BMI, kg / m2 (Me [25; 75]) 40.1 [36.5; 49.6]
FROM, cm (Me [25; 75]) 120 [116; 140]
SBP, mm Hg.Art. (Me [25; 75]) 135 [120; 150]
DBP, mm Hg. (Me [25; 75]) 90 132 90 131 80 [75; 90]
TOC, mmol / L (Me [25; 75]) 4.6 [3.9; 5.7]
HDL, mmol / L (Me [25; 75]) 1.0 [0.8; 1.3]
LDL, mmol / L (Me [25; 75]) 2.4 [2.0; 3.4]
TG, mmol / L (Me [25; 75]) 1.9 [1.5; 3.3]
Ghrelin on an empty stomach, pg / ml (Me [25; 75]) 4.7 [0.2; 13.8]
Ghrelin 120 min after the sample, pg / ml (Me [25; 75]) 5.9 [0.3; 36.0]
GLP-1 fasting, ng / ml (Me [25; 75]) 0.14 [0.07; 0.18]
Leptin on an empty stomach, ng / ml (Me [25; 75]) 3328 [1300; 5400]
Fasting glucose, mmol / l (Me [25; 75]) 9.5 [7.4; 10.4]
HbA1c,% (Me [25; 75]) 8.6 [8.2; 9.0]
C-peptide on an empty stomach, ng / ml (Me [25; 75]) 2.4 [1.9; 4.5]
C-peptide 120 min after the sample, ng / ml (Me [25; 75]) 4.4 [3.3; 6.7]
HOMA-IR, (Me [25; 75]) 5.9 [3.1; 9.0]
HOMA-β (Me [25; 75]) 46.3 [26.8; 83.5]
TG / HDL-cholesterol (Me [25; 75]) 2.5 [1.1; 4.6]

Note: BMI – body mass index; OT – waist circumference; SBP – systolic blood pressure; DBP – diastolic blood pressure; TC, total cholesterol; HDL – high density lipoprotein; LDL – low density lipoprotein; TG – triglycerides; GLP-1 – type 1 glucagon-like peptide; HbA1c – glycated hemoglobin; HOMA-IR – insulin resistance index; HOMA-β – β-cell activity index

In the patients included in the study (9 men and 26 women, age 58 [52.5; 64] years), the duration of T2DM was 10 [5.55; 19.9] years, BMI 40.1 [36.5; 49.6] kg / m2.The HOMA-IR index exceeded normal values ​​(<2.77), and its median was 5.9 [3.1; 9.0]. There were no patients with signs of absolute insulinopenia in the examined group. Despite the long duration of T2DM, the HOMA-β index was 46.3 [26.8; 83.5]. By the nature of therapy, the patients were distributed as follows: only insulin sensitizers (metformin) received 37.2% (n = 13) of the examined, the combination of metformin with sulfonylureas - 31.4% (n = 11) and the combination with insulin - 31.4% (n = 11).

The median fasting ghrelin level before treatment was 4.7 [0.2; 13.8] pg / ml, which is lower than in healthy people (Table 1). In addition, in the post-nutritional status, there was no adequate decrease in the level of ghrelin compared with the baseline – 5.9 [0.3; 36.0] pg / ml, and the change in its level was multidirectional in different patients. Adequate suppression (> 35%) was observed in 42.9% (15/35), insufficient reduction or no change – 28.6% (10/35), an increase – in 28.6% (10/35). At the same time, the level of ghrelin on an empty stomach weakly negatively correlated with body weight (r = -0.3, p <0.05), WC (r = -0.29, p <0.05) and strongly positively (r = 0.63 , p <0.01) - with leptin levels.The level of ghrelin after a standard breakfast also strongly positively correlated with the level of leptin (r = 0.41, p <0.01), moderately negatively - with the level of C-peptide ((r = -0.35, p <0.05) and was sex-related (r = -0.33, p <0.01) .In women, the level of ghrelin after meals was 4.02 [1.81; 16.78] pg / ml and was higher than its level on an empty stomach ( 3.33 [1.96; 4.20]), and in men - 2.53 [2.10; 4.43] pg / ml (p = 0.002 compared to women) and was lower than on an empty stomach 2, 81 [1.87; 7.91] It was also the post-meal ghrelin level that was significantly correlated with the onset of satiety according to the VAS results: between the post-meal ghrelin level and the score for the question “how full do you feel?” negative correlation (r = -0.35, p <0.05).We assessed the relationship between the lack of an adequate decrease in postprandial ghrelin levels with other parameters and found that it occurred in patients with lower fasting ghrelin levels (r = -0.47, p <0.01): fasting ghrelin level in patients with adequate suppression of ghrelin was 4.01 [3.47; 17.50] pg / ml, and in patients with inadequate decrease or abnormal increase - 2.19 [1.01; 3.44] pg / ml (p = 0.01 ). An association was also noted between indicators of glycemic control and a decrease in ghrelin after meals: HbA1c (r = 0.26, p <0.05), glucose (r = 0.28, p <0.05).The median glycemia in patients with an adequate decrease in ghrelin was 7.2 [6.8; 8.8] mmol / L, and in patients with an inadequate response - 8.9 [7.65; 10.0] mmol / L (p = 0.003), and HbA1c - 7.6 [6.8: 9.1]% and 8.4 [7.95; 10.5]%, respectively (p = 0.06). The level of C-peptide after a test with a standard breakfast was significantly higher in patients with adequate suppression of ghrelin (6.11 [4.79; 12.6] ng / ml) than in patients with an inadequate response - 3.1 [2.63 ; 6.26] ng / ml (p = 0.008), as well as the HOMA-β index (66.3 [37.4; 89.5] and 29.3 [16.3; 70.9], respectively, p = 0.04).

The GLP-1 1 level was lower than the reference values ​​in the group as a whole (p = 0.01) and was weakly associated with the severity of hunger: there was a weak negative correlation between its level and the number of points when answering the question “How much do you want there is?” (r = -0.31, p <0.05).

The level of leptin was sharply increased in all examined patients (p = 0.002). Leptin levels strongly positively correlated with age (r = 0.44, p <0.01), moderately negatively correlated with body weight (r = -0.38, p <0.05), BMI (r = -0.35 , p <0.05) and waist size (r = -0.32, p <0.05).Among the studied hormones, except for ghrelin, the level of leptin positively correlated with the level of C-peptide (r = 0.37, p <0.05). Meanwhile, the relationship between leptin level and hunger / satiety, according to the VAS, was rather weak: a weak positive correlation was noted with the number of points when answering the question "How hungry are you?" (r = 0.22, p <0.05) and a weak negative correlation - with the number of points when answering the question "How satisfied are you?" (r = -0.27, p <0.05).

C-peptide levels were significantly associated with hunger and satiety in the VAS.A direct correlation was found between the level of C-peptide on an empty stomach and the number of points when answering the questions “how hungry are you?” (r = 0.47, p <0.01) and "how much are you ready to eat?" (r = 0.34, p <0.05). There was also a weak relationship between the level of C-peptide and body weight (r = 0.28, p <0.05) and OT (r = 0.36, p <0.05), and a stronger relationship with indicators reflecting IR: TG / HDL-C (r = 0.41, p <0.01) and HOMA-IR (r = 0.52, p <0.01).

Patients with mixed (2 or 3 of the studied) and restrictive types of PP predominated in the examined group, no exclusively emotional type was observed.40% (n = 14) had only a restrictive type of PP violation, external – 5.7% (n = 2) and mixed – 54.3% (n = 19) (of which restrictive + external – 2 people, external + emotiogenic – 2 people and a combination of 3 types – 15 patients). It should be noted that the isolated external type of PP (ETPP) was very rare (only 2 patients (men)), and these patients had adequate control (HbA1c <7%) on metformin monotherapy, their HOMA-IR index was significantly lower than in patients of the other two groups with a comparable duration of diabetes (tab.4). Given the small size of this group and the impossibility of an adequate statistical analysis, these patients were excluded from further description.

BMI in patients with restrictive type of PCB (LTBI) was significantly higher than in patients with mixed eating behavior (STBB) (p = 0.04). It should also be noted that there were differences in the nature of therapy between the groups: the percentage of patients receiving monotherapy with metformin was comparable, however, in the OLTT group, half of the patients received a combination with insulin (p = 0.02 with the STPP group), and in the STPP group there was significantly more patients (42.1%) who received a combination with SM drugs (p = 0.02).At the same time, according to the results of assessing the visual analogue scale, the severity of hunger was, on the contrary, higher in patients with STPP (p = 0.04). There was no significant difference in fasting ghrelin levels between the groups with different types of PN (p = 0.65); there was a tendency towards higher leptin levels and lower GLP-1 levels in the OLT group. The post-meal ghrelin level did not differ significantly in patients with different types of PN (Table 3), but the percentage of patients with an adequate decrease in the ghrelin level after meals was significantly higher in the OTI group (p = 0.04).The level of C-peptide on an empty stomach and after a food load did not differ significantly in patients with different types of PN, however, the HOMA-β index turned out to be significantly higher in patients with OLT (p = 0.03), despite a significantly longer period of diabetes (p = 0, 02) (Table 3).

Table 3. Comparative characteristics of patients with different types of eating behavior

901 31 0.03

Parameter / type of PP Restrictive, n = 14 Mixed, n = 19 p
Age, years 58 [52.5; 61] 56 [51; 60.4]
Men / women 2/12 4/15
SD experience, years 17 [7.5; 26] 8 [5; 14.5] 0.02
HbA1c,% 8.2 [7.15; 10.65] 8.2 [ 7.1; 9.4]
BMI before treatment 47.6 [42.5; 55.8] 41.9 [40.1; 50.7] 0, 04
HOMA-IR index 8.05 [5.13; 14.79] 7.6 [4.2; 10.3]
HOMA-β index 61.6 [55.1; 117.1] 39 [26.1; 77.3]
% of patients on SCI 3/14 (21.4%) 8/19 (42.1%) 0.02
% of patients on Mf 4 / 14 (28.6%) 7/19 (36.8%)
% of patients on IT 7/14 (50%) 4/19 (21.0%) 0.02
VAS: How hungry are you? 10 [5; 30] 24 [18; 48.2] 0.04
VAS: How full are you? 27 [17.5; 72.5] 47 [19.2; 75] 0.07
VAS: How much are you hungry? 18 [6; 61.5] 20 [15.8; 70.5]
VAS: How much food could you eat now? 12 [6.5; 43.5] 31 [19; 67.3] 0.04
Leptin, ng / ml 4500 [2300.7; 4920.8] 3200 [2756.8; 4065.2] 0.08
Ghrelin n / t, pg / ml 3.33 [1.98; 4.5] 2.87 [2.07 ; 8.99]
Ghrelin p / e, pg / ml 3.34 [1.8; 5.3] 4.02 [2.02; 12.04]
% of patients with an adequate decrease in ghrelin p / e 57% 41% 0.04
GLP-1 n / t, ng / ml 0.12 [0.11 ; 015] 0.16 [0.11; 0.19] 0.07
C peptide n / t, ng / ml 2.96 [1.7; 4.4] 2.3 [1.9; 5.7]
C peptide p / e, ng / ml 4.8 [3.8; 6.9] 4.0 [3 , 1; 11.8]

Notes: PP – eating behavior, BMI – MA index body weight, PSM – sulfonylurea preparations, Mf – metformin, IT – insulin therapy, GLP-1 – glucagon-like peptide 1, n / t – on an empty stomach, p / f – after meals.

DISCUSSION

The role of appetite hormones – ghrelin, leptin and GLP-1 in the formation of hunger and satiety is beyond doubt and well studied. At the same time, the relationship between hormonal changes in severe obesity and T2DM with the nature of PP disorders is under study, and the number of works on this topic is not numerous. Most obese people are in a state of chronic stress and have emotional-affective disorders that make a significant contribution to the formation of PP disorders [3, 15].Meanwhile, in studies that studied the prevalence of various types of PP impairment in T2DM, there was a lower incidence of emotiogenic type of PN impairment, in particular, “food drinking”, in this group compared to both patients with type 1 diabetes [17] and obesity without SD [11]. In contrast, OLTI is more common in patients with T2DM and obesity than in obese patients without diabetes [11]. Our study, which studied the nature of PP impairment in patients with severe obesity in combination with T2DM, revealed similar tendencies: an isolated variant of the emotiogenic type of PP impairment did not occur, and the most frequent was OLTC.More than half of the patients had STPP. In a study by L.A. Zvenigorodskaya et al. [18], who studied the incidence of various types of PN in patients with abdominal obesity and metabolic syndrome of various ages, the most frequent was ETPP (44% of patients), the most rare was the emotiogenic type of PN (20% of the examined), and OLT was in 36%. In the group examined by us, more than half of the patients had a combination of various types of PN, and in isolated form, OLT was most often found, which was detected in 40% of patients.This may indicate a more complex pathogenesis of PP disorders in patients with T2DM, as well as reflect differences in the sample and methodological approach. Since the mixed type of PP was not mentioned in the cited study, the authors probably determined the type of PP by the dominant variant. This study also analyzed two of the three hormones we studied that regulate PP – leptin and ghrelin, but the results obtained differ from those obtained in our study. The authors of this work noted that the level of ghrelin was significantly higher than normal in all patients, and the highest level was observed in patients with OLT.Meanwhile, in numerous studies it is noted that obese patients are characterized by the development of ghrelin resistance, and their fasting ghrelin level is usually low [10], as was the case in the patients of the studied group. As well as other authors, we noted a negative correlation of fasting ghrelin level with BMI and parameters indirectly characterizing visceral obesity (OT, HOMA-IR index). At the same time, there were no significant differences in the fasting ghrelin level in the patients examined by us with different types of PN.The contradictions in the data obtained may be associated with differences in the surveyed groups. In the study of L.A. Zvenigorodskaya et al. [18] predominantly included patients with overweight and mild obesity. Our study included patients with higher degrees of obesity. As noted earlier, ghrelin resistance correlates with BMI, and higher ghrelin levels in L.A. Zvenigorodskaya can be explained by this. In addition, other factors can influence fasting ghrelin levels.Thus, the decrease in the duration of sleep is 2-3 hours less than the norm (7 hours) for 2 days. can increase the production of ghrelin by more than 15%, and systematic sleep deficit increases the level of ghrelin by 35% [19]. We focused the attention of patients on the importance of a normal duration of sleep before the examination, which made it possible to neutralize the effect of this factor. Ambient temperature can also matter – cooling results in an increase in ghrelin levels. In women of reproductive age, ghrelin levels differ significantly in different phases of the menstrual cycle, since high estradiol levels suppress ghrelin production [20].In our study, the effect of these factors was also taken into account: patients were examined at a stable air temperature, and among the examined there were only 3 women of reproductive age who were examined in the luteal phase of the menstrual cycle to minimize the effect of changes in estradiol levels. Post-food ghrelin levels have not been studied in the cited work [18], but according to the majority of studies presented in the literature, patients with obesity, IR and T2DM have a decrease in the amplitude or no change in the level of ghrelin after meals compared with people with normal body weight [10].In our study, the majority of patients also showed disturbances in the post-food decrease in the level of ghrelin, although the changes were multidirectional. Adequate decrease in the level of ghrelin after eating was in 42.9% of the examined patients. More often, an adequate decrease in the level of ghrelin after meals was noted in patients with OLTD (57%). Failure to adequately reduce postprandial ghrelin was associated with decreased satiety and poorer glycemic control, combined with lower β-cell reserve. The leptin level in the examined group was significantly higher than the norm, which coincides with the data of other studies demonstrating a high level of leptin in obese patients [10].We found no significant differences in leptin levels in patients with different types of PN. In a study by L.A. Zvenigorodskaya et al. [18] the highest level of leptin was noted in the group with ETPP, which was not included in the analysis in our study due to its small number. It should also be noted that the patients in our group were significantly older. It is known that the level of leptin changes with age, and we have also noted this connection.

Despite high levels of leptin, its relationship with the severity of hunger and satiety, according to the VAS, was rather weak, which once again demonstrates the presence of resistance to leptin in patients with severe obesity, IR and T2DM.However, the level of leptin strongly positively correlated with the level of ghrelin in our study, which is not consistent with all studies. Some authors also noted a positive relationship between the level of ghrelin and leptin [18], in other studies, multidirectional changes in their level in obesity were noted [20].

Summing up, we can note significant differences in the incidence of various types of PP impairment in patients with T2DM and metabolic syndrome without T2DM. Meanwhile, the volume of studies that have studied the relationship of various types of PP impairment with the level of appetite hormones is small, and further studies on large samples are required to clarify its structure.

A limitation of our study is the small sample size.

CONCLUSION

The severity of resistance to leptin and ghrelin correlated with each other in patients with T2DM and BMI> 35 kg / m2, and the severity of resistance to ghrelin also correlated with the functional state of β-cells. The post-nutritional level of ghrelin had multidirectional changes in patients with T2DM and obesity, and its adequate decrease was more typical for patients with OLT.

Patients with different types of eating disorders showed a tendency to differences in the level of hormones that regulate appetite, which did not reach significant differences in our group, which may be due to the small number of patients examined.

ADDITIONAL INFORMATION.

Funding source. The study was supported by the Russian Science Foundation grant 17-75-30052.

Conflict of interest. The authors declare no obvious and potential conflicts of interest related to the publication of this article.

References Kemps E, Herman CP, Hollitt S, et al. The role of expectations in the effect of food cue exposure on intake. Appetite. 2016; 103: 259-264. doi: 10.1016 / j.appet.2016.04.026.Travagli RA, Anselmi L. Vagal neurocircuitry and its influence on gastric motility.Nature Reviews Gastroenterology & Hepatology. 2016; 13 (7): 389-401. doi: 10.1038 / nrgastro.2016.76. Ziauddeen H, Alonso-Alonso M, Hill JO, et al. Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake. Advances in Nutrition. 2015; 6 (4): 474-486. doi: 10.3945 / an.115.008268. Engel JA, Jerlhag E. Role of Appetite-Regulating Peptides in the Pathophysiology of Addiction: Implications for Pharmacotherapy. CNS Drugs. 2014; 28 (10): 875-886. doi: 10.1007 / s40263-014-0178-y. Adamska E, Ostrowska L, Górska M, Krętowski A.The role of gastrointestinal hormones in the pathogenesis of obesity and type 2 diabetes. Gastroenterology Review. 2014; 2: 69-76. doi: 10.5114 / pg.2014.42498 Ronveaux CC, Tomé D, Raybould HE. Glucagon-Like Peptide 1 Interacts with Ghrelin and Leptin to Regulate Glucose Metabolism and Food Intake through Vagal Afferent Neuron Signaling. The Journal of Nutrition. 2015; 145 (4): 672-680. doi: 10.3945 / jn.114.206029. Howick K, Griffin B, Cryan J, Schellekens H. From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation.International Journal of Molecular Sciences. 2017; 18 (12): 273. doi: 10.3390 / ijms18020273 Shiiya T. Plasma Ghrelin Levels in Lean and Obese Humans and the Effect of Glucose on Ghrelin Secretion. J. Clin. Endocrinol. Metab. 2002; 87 (1): 240-244. doi: 10.1210 / jcem.87.1.8129. St-Pierre DH, Rabasa-Lhoret R, Lavoie ME, et al. Fiber intake predicts ghrelin levels in overweight and obese postmenopausal women. European journal of endocrinology / European Federation of Endocrine Societies. 2009; 161 (1): 65-72. doi: 10.1530 / eje-09-0018. St-Pierre DH, Karelis AD, Coderre L, et al. Association of Acylated and Nonacylated Ghrelin with Insulin Sensitivity in Overweight and Obese Postmenopausal Women. J. Clin. Endocr. Metab. 2007; 92 (1): 264-269. doi: 10.1210 / jc. 2006-1603. Mannucci E, Tesi F, Ricca V, et al. Eating behavior in obese patients with and without type 2 diabetes mellitus. Int. J. Obes. 2002; 26 (6): 848-853. doi: 10.1038 / sj.ijo.0801976. Inui A. Preface [Hot Topic: Medicinal Strategies in the Treatment of Obesity (Guest Editor: Akio Inui)].Current Medicinal Chemistry – Central Nervous System Agents. 2003; 3 (3): 1-2. doi: 10.2174 / 1568015033477767. Covasa M, Swartz T. The Role of Glucagon-Like Peptide-1 (Glp-1) in Eating Behavior. 2011: 189-201. doi: 10.1007 / 978-0-387-92271-3_14. Rask E, Olsson T, Soderberg S, et al. Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men. Diabetes Care. 2001; 24 (9): 1640-1645. doi: 10.2337 / diacare.24.9.1640. Sominsky L, Spencer SJ. Eating behavior and stress: a pathway to obesity.Front. Psychol. 2014; 5. doi: 10.3389 / fpsyg.2014.00434 Buss J, Havel PJ, Epel E, et al. Associations of ghrelin with eating behaviors, stress, metabolic factors, and telomere length among overweight and obese women: Preliminary evidence of attenuated ghrelin effects in obesity? Appetite. 2014; 76: 84-94. doi: 10.1016 / j.appet.2014.01.011. Mannucci E, Rotella F, Ricca V, et al. Eating disorders in patients with Type 1 diabetes: A meta-analysis. J. Endocrinol. Invest. 2014; 28 (7): 417-419. doi: 10.1007 / bf03347221.Zvenigorodskaya L.A., Kucherenko T.V. Types of eating behavior and hormones of eating behavior in patients with metabolic syndrome.