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Aim. Evaluation of genes polymorphisms frequencies of angiotensinogen (AGT), angiotensin converting enzyme type 1 (ACE1) and angiotensin II receptors type 1 (AGTR1) and type 2 (AGTR2) in patients admitted with coronavirus disease (COVID-19) and its association the severity of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2). Materials and methods. The study included 100 patients admitted to the hospital with a laboratory-confirmed diagnosis of COVID-19. All patients were identified with alleles and genotypes of polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene. The frequencies of each polymorphisms were compared with population. Statistical processing was performed using the Statistica 8.0 software package. Results. In evaluated cohort there was higher frequency of D-allele ACE1 rs1799752 compared to population. Depending on the availability of criteria for the severity of coronavirus infection, 44 (44%) patients were diagnosed with severe, 56 (56%) with moderate course. The groups did not significantly differ in age, gender, cardiovascular risk factors and comorbid pathology. In the groups with severe and moderate course, the same distribution of genotypes and alleles of AGT rs4762, AGTR2 rs1403543 and ACE1 rs1799752 was revealed. For the I/D alleles of the ACE1 rs1799752 gene, a significant deviation from the papulation was found in both the group of severe and moderate COVID-19. In the group with a severe course of the disease, a higher frequency of the mutant C-allele of the AGTR1 rs5186 gene was detected. In the same group, a deviation in the frequency ratio of A and C of the AGTR1 rs5186 alleles from Hardy–Weinberg Equilibrium was found. When calculating the risk of severe COVID-19 in the presence of the C-allele compared with the A-allele, an odds ratio 2.092 (95% confidence interval 1.066–4.108) was obtained. Conclusion. The data obtained suggest that the genes polymorphisms of the components of renin-angiotensin-aldosterone system, namely D-allele of ACE1 rs1799752 and C-allele of AGTR1 rs5186, may make it possible to identify groups of patients predisposed to the development of more severe COVID-19.

Currently, increasing evidence shows the mutual influence of aldosterone and adipose tissue. Aldosterone excess has been reported in patients with obesity and metabolic syndrome. Aldosterone has a direct effect on adipose tissue increasing anabolic activity and expression of mineralocorticoid receptors. In turn, excessive activation of MCR leads to stimulation of adipogenesis and an increase in the volume of adipose tissue. Aldosterone excess can be considered an independent cardiovascular risk factor that affects such processes as cardiac fibrosis, nephrosclerosis, and arteriosclerosis. There is convincing evidence of higher prevalence and severity of impaired glucose homeostasis and lipid metabolism disorders among patients with primary hyperaldosteronism. Similar pathological changes are also observed in patients with obesity and metabolic syndrome. This review presents scientific data on the metabolic effects of aldosterone, in particular its effect on adipose tissue function, glucose and lipid metabolism. Treatment with mineralocorticoid receptor antagonists may provide substantial benefit in the management of metabolic syndrome, contribute to the stabilisation of glucose and lipid metabolism, improve clinical status of patients with cardiovascular diseases and reduce the risk of complications. However, available evidence from the conducted studies is not sufficient to justify introduction of such therapy into clinical practice.

The renin-angiotensin-aldosterone system (RAAS) activation plays a key role in the chronic kidney disease (CKD) progression and in the cardiovascular complications (CVC) development in patients with diabetes mellitus (DM). RAAS blockers alone are not sufficient to prevent CVC and CVC progression. RAAS upregulation in CKD associated with DM triggers the mineralocorticoid receptors (MCR) hyperactivation which results in fibrosis and inflammation in the heart and kidneys. This review presents the current data about the variety of MCR hyperactivation manifestations, as well as about of multiplicity of MCR hyperactivation ways in DM. The efficacy and safety of finerenone, a new MCR nonsteroidal selective antagonist, are discussed.

One in four people in the world currently has kidney problems to varying degrees. It is known that the new coronavirus infection (COVID-19) is primarily a respiratory disease, but the kidneys are the target organ. Coronavirus is tropic to renal tissue due to the presence in the organ of the angiotensin converting enzyme type 2 and transmembrane serine protease 2, which are considered the target of this virus. The presence of any stage of renal insufficiency is an independent adverse risk factor for coronavirus infection and results in high hospitalization rates in hospitals and a mortality rate. Kidney damage is caused by a variety of pathogenetic mechanisms: direct cytopathic effect of the virus on their structure (in the kidney body - podocytes, mesangial cells, in the vascular glomerulus - endothelium of capillaries, in the proximal tubules - epithelial cells); cytokine storm; damage to the renin-angiotensin-aldosterone system; immunothrombosis. In many patients with confirmed coronavirus infection, significant changes in urine analysis (hematuria, proteinuria) and an increase in serum creatinine levels have been observed in the laboratory since the first days of the disease. One of the main risk factors for mortality is the development of acute renal injury. More research is needed on the exact effects of SARS-CoV-2 on the kidneys. Understanding the main pathogenetic pathways of kidney damage in COVID-19 is necessary for the development of strategies and the development of effective treatment methods.

This article deals with current issues of pharmacotherapy of cardiovascular diseases which are based on disfunction of the renin-angiotensin-aldosterone system. As compared with the efficacy and safety of two major classes of drugs for the pharmacotherapy of cardiovascular diseases — angiotensin II receptor blockers and ACE inhibitors — are given data from clinical trials of both classes of drugs.

Background. The relationships between renin-angiotensin-aldosterone system (RAAS) and elevated parathyroid hormone levels in primary hyperparathyroidism (PHPT) is being actively discussed. But the way how parathyroid hormone interacts with renin and aldosterone currently is not clear. Materials and methods. Forty patients aged 18 to 70 years with a confirmed diagnosis of PHPT were involved in the study. All patients were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin, plasma aldosterone) before and 2 weeks after parathyroidectomy. Results. Sixty percent of patients had any cardiovascular disease (CVD) and hypertension was the most common. Patients CVD in comparison with patients without CVD were older (61 and 41 years, respectively; p0.001), had a higher body mass index (28.9 and 21.9 kg/m2, respectively; p0.001) and had a lower aldosterone-to-renin ratio ARR (1.78 and 5.42, respectively; p=0.030). Patients with hypertension were older than patients with normal blood pressure (63 and 41 years, respectively; p0.001), had a higher body mass index (28.1 and 23.5 kg/m2, respectively; p=0.005), a lower ARR (1.46 and 5.82, respectively; p=0.001), as well higher levels of plasma renin (109.2 and 20.3 pg/ml, respectively; p=0.007) and serum total calcium (2.84 and 2.71 mmol/l, respectively; p=0.041). Correlation analysis showed that in patients with PHPT and CVD, the concentration of aldosterone is associated with the level of 24-hour urinary calcium (r=0.829, p=0.042), and in patients with symptomatic PHPT and CVD, the level of aldosterone correlated with the level of ionized calcium (r=-0.812, p=0.05). We found no significant differences between the levels of renin, aldosterone and ARR before and 2 weeks after parathyroidectomy. However, in the postoperative period, there were no differences in the levels of renin and ARR among patients with hypertension and without hypertension. Conclusion. In our study we found that the levels of plasma renin and serum total calcium were higher in patients with PHPT and hypertension compared to patients with normal blood pressure. Also, we found the associations between plasma aldosterone and levels of ionized calcium and 24-hour urinary calcium. But the relationships between RAAS parameters and parameters of phosphorus-calcium metabolism need further investigations.

Introduction. The development of a malignant tumor naturally affects renal function. During tumor formation, the renal tissue is destructed either by direct invasion into the parenchyma, or by mechanical change in the renal architecture caused by compression of the renal parenchyma, collecting ducts, tubules, and nephrons. In addition, a tumor can secrete biologically active substances, which have an indirect negative influence the functional state of the organ. Currently, it has been established that kallikrein-kinin and renin-angiotensin-aldosterone systems play an important role in the development of nephropathy of various genesis. At the same time, these systems' role in the development of renal function disorders in the setting of tumor damage has not yet been studied.Purpose of the study. To study changes in the components of the kallikrein-kinin and renin-angiotensin-aldosterone systems in the case of localized kidney cancer.Materials and methods. Forty-five patients diagnosed with T1N0M0 kidney cancer and 13 relatively healthy patients without cancer were examined. The determination of the components of the systems under study was carried out by the kinetic method after chromatography of blood plasma and urine using DEAE-Sephadex A-50 (Amersham Biosciences Corp., Sweden). The indices of angiotensin-1, renin, aldosterone, and cortisol were studied by an indirect method of radioimmunoassay. Statistical processing was carried out using Statistica 8.0 software (StatSoft Inc., IBM Corp., USA) by means of the Student-Fisher test (p < 0.05).Results. The development of kidney cancer is accompanied by a 2.3-fold increase in the activity of kallikrein and other trypsin proteases with a significant deficiency of their inhibitors (p < 0,05). Against this background, there is a 1.3-fold decrease in the cortisol/renin ratio from a 2.9-fold and 2.3-fold increase in the values of the renin/angiotensin-I and cortisol/angiotensin-I interaction ratios, respectively, compared with the normal values of these indicators (p < 0,05).Conclusions. Renal cell carcinoma is accompanied by trespassing of local metabolism with the formation of tubulointerstitial dysfunction and a shift of the proteinase-inhibitory balance towards proteolytic activation.

Aim: Evaluation of genes polymorphisms frequencies of angiotensinogen (AGT), angiotensin converting enzyme type 1 (ACE1) and angiotensin II receptors type 1 (AGTR1) and type 2 (AGTR2) in patients admitted with coronavirus disease (COVID-19) and its association the severity of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)., Materials and Methods: The study included 100 patients admitted to the hospital with a laboratory-confirmed diagnosis of COVID-19. All patients were identified with alleles and genotypes of polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene. The frequencies of each polymorphisms were compared with population. Statistical processing was performed using the Statistica 8.0 software package., Results: In evaluated cohort there was higher frequency of D-allele ACE1 rs1799752 compared to population. Depending on the availability of criteria for the severity of coronavirus infection, 44 (44%) patients were diagnosed with severe, 56 (56%) with moderate course. The groups did not significantly differ in age, gender, cardiovascular risk factors and comorbid pathology. In the groups with severe and moderate course, the same distribution of genotypes and alleles of AGT rs4762, AGTR2 rs1403543 and ACE1 rs1799752 was revealed. For the I/D alleles of the ACE1 rs1799752 gene, a significant deviation from the papulation was found in both the group of severe and moderate COVID-19. In the group with a severe course of the disease, a higher frequency of the mutant C-allele of the AGTR1 rs5186 gene was detected. In the same group, a deviation in the frequency ratio of A and C of the AGTR1 rs5186 alleles from Hardy-Weinberg Equilibrium was found. When calculating the risk of severe COVID-19 in the presence of the C-allele compared with the A-allele, an odds ratio 2.092 (95% confidence interval 1.066-4.108) was obtained., Conclusion: The data obtained suggest that the genes polymorphisms of the components of renin-angiotensin-aldosterone system, namely D-allele of ACE1 rs1799752 and C-allele of AGTR1 rs5186, may make it possible to identify groups of patients predisposed to the development of more severe COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared the cause of a global pandemic in early 2020. Patients with COVID-19 are at high risk for thrombotic occlusions of the arteries and veins. There are many ways that explain the high risk of thrombosis in COVID-19, they are conditionally divided into two main categories: mechanisms in which the renin-angiotensinaldosterone system is involved and mechanisms that affect the regulation of the immune response. It is assumed that the uncomplicated course of the disease is characterized by endothelial dysfunction, but if the process progresses with a pronounced immune response, plasma coagulation factors may also be involved, which significantly increases the risks of thromboembolic complications. The use of combined hormonal contraception (CHC) in the current conditions raises a number of concerns. According to some researchers, disorders of the hemostasis system observed in patients with COVID-19 may worsen while taking CHC and increase the risk of thromboembolic complications, which is especially important in severe disease with prolonged immobilization. However, with the use of CHC, the increase in thrombotic risks is explained primarily by changes in the plasma component of the hemostasis sys tem. At first glance, the recommendations to stop hormone therapy with confirmed COVID-19 seem logical, but they are based only on the procoagulant activity of estrogens, and not on real evidence. In patients with COVID-19, the increase in coagulation is associ ated with massive damage to the vascular endothelium (the so-called «external» coagulation pathway) and the immune response, and not with a primary increase in the level of coagulation factors per se. At the same time, stopping the intake of estrogens deprives the patient of their important protective effect. Thus, it became necessary to develop clinical guidelines for the management of women using contraception in the context of the COVID-19 pandemic.

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Arterial hypertension was one of the most common comorbidities associated with a high risk of death in hospitalized patients with COVID-19. Patients with hypertension are routinely and according to standards treated with angiotensinconverting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARB) II. ACE inhibitors or ARB II are included in fixed combinations of antihypertensive drugs recommended for patients with uncomplicated hypertension, as well as when combined with various comorbidities. During the COVID-19 pandemic, there were suggestions about the potential for a negative effect of drugs of these classes on the course and outcomes of a new coronavirus infection. There was a need for a quick response from the most reputable medical organizations to the question of the use of ACE inhibitors and ARB II during the COVID-19 pandemic. The expert position was soon published despite the lack of evidence from randomized clinical trials. Was there any reason for concern about the treatment of ACE inhibitors and ARB II for COVID-19? What are the relationships between the renin-angiotensin-aldosterone system (RAAS) and COVID-19? Is there any new data from clinical trials that can confirm or deny the previously presented position of professional societies regarding the use of RAAS blockers in COVID-19? What is the role of the difference in the mechanism of action of an ACE inhibitor and ARB II in COVID-19? Is it possible that RAAS blockers will be helpful in treating COVID-19? Will the tactics of hypertension pharmacotherapy change in the near future? In this review article, modern concepts on this problem are discussed and answers to the listed questions reflecting the achieved level of knowledge are formulated.

Aim. To study the dependence of the effectiveness of antihypertensive therapy on the polymorphic variants of candidate genes of the RAAS (ACE, AGT, AGTR1) in patients with hypertension (АH) of the population of Mountain Shoria. Materials and methods. In the conditions of the expeditions from 2013 to 2017, the population of Mountain Shoria was surveyed. Included 1409 people 18 years and older. Blood pressure monitoring was carried out as a result of office measurement, according to the standard recommendations of National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). As a result of the survey, patients with AH were identified for further observation (597 people) who need medical antihypertensive treatment. Repeat screening was conducted in a year. The criterion for inclusion in prospective observation of patients with hypertension was: regular intake of prescribed medication. 253 respondents were surveyed: indigenous (156 people) and non-indigenous (97 people) nationality. All patients underwent a standard examination, including the collection of complaints and anamnesis, an assessment of objective status, laboratory and instrumental studies. Polymorphisms of genes ACE (I/D, rs 4340), AGT (c.803T C, rs699), AGTR1 (A1166C, rs5186) were tested using polymerase chain reaction. Results. Dynamic observation of patients with hypertension found that in the cohort of Shors the target level of blood pressure reached the owners of heterozygous I/D and minor D/D genotypes of the ACE gene, carriers of T/C and C/C genotypes of the AGT gene and the homozygous genotype A/A of the AGTR1 gene. In the non-indigenous nationality cohort, only carriers of the D/D genotype of the ACE gene. Conclusion. National differences were identified with respect to the sensitivity of the pharmacological response to treatment, which once again proves the important role of taking into account the ethnic factor in the choice of drug.

In the development of renocardial relationships in chronic kidney disease, an important role is given to the activation of the renin-angiotensin-aldosterone system (RAAS), as the main component of the progression and development of cardiovascular complications..The presented review is devoted to the analysis of modern scientific data on the effect of high RAAS activity in chronic kidney disease on the course and prognosis of cardiovascular complications, as well as the protective capabilities of angiotensin-converting enzyme inhibitors, in particular perindopril. The results of scientific research on the role of the RAAS in the progression of chronic kidney disease are summarized. Data on chronic kidney disease as a risk factor for cardiovascular and cerebral complications are presented. Attention is focused on the possibilities of prolonging the pre-dialysis period of chronic kidney disease when using angiotensin-converting enzyme inhibitors. The role of perindopril as a lipophilic angiotensin-converting enzyme inhibitor with a high affinity for tissue RAAS was emphasized in reducing cardiovascular and cerebral risk in chronic kidney disease.

Objective: to evaluate the effect of renin-angiotensin-aldosterone system (RAAS) blockers on aldosterone level in patients with chronic heart failure with preserved ejection fraction (HFpEF).Materials and methods: the prospective study included 158 patients (58 men and 100 women, mean age 62,3 ± 7,4 years) with HFpEF (> 50 %) and left ventricular diastolic dysfunction. All patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. We evaluated the duration of treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-2 receptor antagonists (ARA-2) and its average daily dose. The dose of RAAS blockers was assessed during previous 6 months as a percentage of target. Aldosterone plasma concentration was measured and the normal level was 40 – 160 pg/ml.Results: according to laboratory results 99 patients (62,7 %) had normal aldosterone level (nAld) and 59 patients (37,3 %) had high aldosterone level (hAld). hAld patients had significantly higher duration of RAAS blockers treatment (6 (3; 8) versus 4 (2; 5) years, p < 0,001) and dose (50 (25; 50) % vs 25 (12,5; 50) % of target, р=0,01). Multiple regression analysis showed that after standartization for age, severity of HFpEF, duration of arterial hypertension and comorbidity only long-term (more than 5 years) treatment with RAAS blockers remained the independent risk factor of high aldosterone level (odds ratio 3,16, 95 % confidence interval 2,08 – 8,24).Conclusions: in HFpEF patients’ plasma aldosterone level is closely associated with RAAS blockers treatment. Long-term (more than 5 years) therapy with ACE inhibitors or ARA-2 is the independent risk factor of secondary hyperaldosteronism.

A review of current publications suggests that patients with arterial hypertension (AH) are at increased risk for severe course and fatal outcome of COVID-19. The main pathogenetic mechanisms explaining the association of AH with COVID-19 include the effect of coronavirus on the functioning of the renin-angiotensin-aldosterone system (RAAS), which is involved in the development and progression of AH. The review presents the results of a number of studies evaluating the effect of the use of ACE inhibitors / ARBs on the development and course of COVID-19 in patients with cardiovascular diseases. The results of international data analysis showed that the use of ACE inhibitors / ARBs in patients with AH and COVID-19 is associated with lower rates of total mortality, and the use of ACE inhibitors, statins and the female sex are associated with a greater likelihood of patient survival. The data on the promising development of new drugs affecting the functioning of RAAS are presented.

Aim.To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE). Materials and methods.A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity PRA, serum aldosterone, angiotensin II AT II). Results.Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090;p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed. Conclusion.In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.

In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task. Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension. Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators. Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.

Objectives to study the indicators of humoral regulation of circulatory system in obese patients as the predictors of CHF development. Materials and methods.Two groups of 40 patients were formed: the first group consisted of patients with I or II grades obesity with BMI of up to 40 kg/m2, the second group included patients with grade III obesity with BMI of over 40 kg/m2. None of the selected patients had a history of cardiovascular events. The concentration value of renin-angiotensin-aldosterone system components and level of N-terminal pro B-type natriuretic peptide (NT-pro-BNP) was determined. Results.Aldosterone level in grade III obese patients was close to normal upper border: 58.9 [54.9; 73.8] pg/ml (normal range is 1060 pg/ml), while in patients with grade III obesity it was 79.5 [64.5; 90.1], which is 25.9% higher than in patients of the first group and 24.5% higher above the normal level (p 0.05). These two groups was significantly different not only in average plasma aldosterone level, but in absolute number of patients with hyperaldosteronism, whose number accounted for 46.2% in grades I or II obese patients and 85.7% among patients with grade III obesity. Plasma renin level and angiotensin II levels in both groups was within the normal range. NT-proBNP level in the first group was 23.7 [10.6; 23.6] pg/ml, in the second group 138.0 [121.5; 145.9] pg/ml, which is 5.8 times higher (p = 0.001). In both groups of patients, the correlation analysis showed that aldosterone and NT-proBNP levels are closely related (r = 0.74, p 0.05). Conclusion.This study suggests that aldosterone level can be used as a predictor of HF.

BACKGROUND: Type 2 diabetes and arterial hypertension are frequent comorbidities under which activation the renin-angiotensin-aldosterone system is important pathogenetic link. The functional state of the RAAS is genetically determined. Genetic polymorphisms of the RAAS system associated with the development of both type 2 diabetes and arterial hypertension have been identified and mapped. Associations of polymorphic variants of the RAAS genes with type 2 diabetes and arterial hypertension among the inhabitants of Dagestan have not been studied. AIM: Studying the association of the most relevant polymorphic variants of the C521T and T704C AGT gene, as well as the A1166C AGTR1 gene with type 2 diabetes and when combining type 2 diabetes with arterial hypertension among Dagestan inhabitants. METHODS: We examined 16 patients with type 2 diabetes, 59 patients with type 2 diabetes combined with arterial hypertension and 51 patients with arterial hypertension, all residents of Dagestan. The control group included 47 healthy persons of the same age group. SNP polymorphisms were investigated by the method of allele-specific Real-Time PCR. The C521T and T704C polymorphisms of the AGT gene and the A1166C polymorphism of the AGTR1 gene were studied. RESULTS: In the group of patients with a combination type 2 diabetes with arterial hypertension, the genotype CT of the C521T polymorphism of the AGT gene is less common compared to the control (23% vs. 43%, χ2 = 3,868, p = 0,049), OR score – 0,4 (0,2-0,9 ). The situation is similar with the TC genotype of the T704C polymorphism of the AGT gene (39% versus 61%, χ2 = 4,282, p = 0,039). OR was 0,4 (0,2–0,8).On the contrary, in the same patients, but the carriers of the homozygous CC genotype of the T704C polymorphism of the AGT gene, OR exceeded one and made 2.5 (1.02-5.9), the frequency of occurrence was 42% vs. 23%, χ2 = 3,363, p = 0,05. The frequency of the mutant allele C of the A1166C polymorphism of the AGTR1 gene in patients with arterial hypertension alone was 31% vs. 14%, χ2 = 5.496, p = 0,019, OR – 2,5 (1,2-5,0). The frequency of the wild allele A in these same patients was 69% versus 84%, χ2 = 5,496, p = 0,019, OR – 0,4 (0,2-0,8). A similar situation is determined with the AA genotype (52% versus 73%, χ2 = 3,609, p = 0,05), OR = 0,4 (0,1-0,9). CONCLUSIONS: The association of the C521T and T704C polymorphisms, as well as the A1166C candidate genes AGT and AGTR1 with type 2 diabetes and arterial hypertension, is an important component in assessing the susceptibility to the development of these diseases in Dagestan residents.

Aim. To study the associations of angiotensinogen (AGT) (s4762(С521Т), rs699(Т704C)) and angiotensin II receptor type I (AGTR1) (rs5186(A1166C)) genetic polymorphisms with serum levels of insulin, glucagon, C-peptide, leptin, as well as with dyslipidemia and glycemic levels in Dagestan residents with combination of type 2 diabetes (T2D) and hypertension (HTN), as well as with isolated T2D/HTN.Material and methods. We examined 16 patients with isolated T2D, 59 patients with T2D+HTN and 51 patients with isolated HTN from Dagestan. Genetic polymorphisms of the AGT and AGTR1 genes were studied. The levels of insulin, glucagon, C-peptide, and leptin were studied by enzyme-linked immunosorbent assay (ELISA), while lipid and carbohydrate metabolism — by biochemical methods.Results. In patients with T2D, the association of CC genotype of AGT gene rs4762(С521Т) polymorphism with a leptin decrease was determined, while its CT genotype was associated with an increase in serum level of triglycerides. The TC genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in leptin, triglyceride and glucose levels. The AA genotype of AGTR1 gene rs5186(A1166C) polymorphism was associated with an increase in insulin and glucose levels, as well as a decrease in leptin level. In patients with a combination of T2D and HTN, CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism was associated with a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in insulin, triglyceride, glucose and body mass index (BMI) levels. In isolated HTN, the CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism were associated ith a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with increased levels of insulin, low density lipoproteins, and BMI.Conclusion. Associations of AGT (s4762(С521Т), rs699(Т704C)) and AGTR1 (rs5186(A1166C)) genetic polymorphisms with carbohydrate and lipid metabolism changes are an important pathogenetic link of T2D and HTN, which allows developing an individual prognosis of these diseases in Dagestan residents.

Atrial fibrillation (AF) is one of the most common cardiac rhythm disorders. Its prevalence is about 1 % in the general population and exceeds 7 % in individuals older than 60 years of age. It is known that hyperactivation of the renin-angiotensin-aldosterone system plays a key role in structural and electrical myocardial remodeling in AF. Increased activity of the renin-angiotensin-aldosterone system causes inflammation, fibrosis and oxidative stress in cardiomyocytes. Last studies suggest that most of negative effects previously explained by angiotensin-2 may be particularly caused by excessive aldosterone activity. More data about extra-adrenal hormone production (in the myocardium, the vascular wall and even the brain) have appeared, and its receptors were found far beyond the kidneys — in cardiomyocytes, endothelial cells, fibroblasts, monocytes, and macrophages. It was also shown that aldosterone has a wide profile of pathogenic effects, one of which is the stimulation of atrial myocardial fibrosis as the structural basis for AF. The discovery of new features of aldosterone suggests that blockade of mineralocorticoid receptors may prevent or slow down atrial remodeling and thereby reduce the incidence of AF. The article presents data of the world literature and the results of own studies devoted to the use of mineralocorticoid receptor antagonists in patients with AF. Modern concepts of the role of aldosterone in the arrhythmia development and the main approaches of upstream-therapy are described. The possibilities of using eplerenone and spironolactone in primary and secondary prevention of AF are discussed.

One of the important medical and social present-day problems is atrial fibrillation (AF) which prevalence in the adult population is 2 % for persons under 65 and 9 % for those over 65 years of age and it is a common cause of ischemic stroke. The embolic complications incidence is 2.1 % per year in patients with paroxysmal AF, and 3.0 % per year in patients with persistent AF. The aim of the study is to analyze the modern literary sources related to the role of gene polymorphisms regulating some neurohumoral systems in group of patients with atrial fibrillation. A combination of certain genes polymorphisms can contribute to AF risk. Especially important are gene studies of the renin-angiotensin-aldosterone system (RAAS) role in the pathogenesis of AF which are currently being studied with a particular intensity. Recent data show that activation of RAAS plays an important role in the development and recurrence of AF. These studies are of great practical interest as the associative effect of angiotensin converting enzyme (ACE) inhibitors in the prevention of AF has been identified. AGT gene encodes a plasma protein known as angiotensinogen. This protein is expressed in the liver and is cleaved by the enzymatic renin action in response to lower blood pressure. The resulting product, angiotensin I, is then cleaved by ACE to the physiologically active enzyme angiotensin II. Defects in this gene may also be associated with non-hereditary AF. More than 16 spot mutations in the AGT gene were discovered, most of which resulted in amino acid substitutions. Conclusions. The analysis of the literature allows to conclude that, first, genetic polymorphisms may influence both the severity of pathological changes in the body and the efficacy of pharmacotherapy, and second, the study of RAAS gene polymorphisms may allow early detection of persons with increased risk of persistent AF recurrence and its prevention.

The review of literature presents modern ideas about the role of aldosterone in the development and maintenance of atrial fibrillation. It is shown that hormone takes part in all stages of the electrophysiological and structural atrial remodeling, contributing to the formation of the arrhythmia substrate. It was noted that adverse effects of the aldosterone in the myocardium are realized not only due to its high systemic production but also because of its direct synthesis in the atrial tissues. Increased expression of mineralocorticoid receptors in cardiomyocytes also play important role in the development of atrial fibrillation. It is demonstrated that hyperaldosteronemia can be a cause as well as effect of atrial fibrillation. The episode of arrhythmia is characterized by neurohormonal activation, increased intramyocardial aldosterone synthesis and high mineralocorticoid receptors expression. This contributes to the further progression of atrial remodeling and makes conditions for the arrhythmia recurrences.

Aim. To compare the effects of 3-month therapy with a fixed-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a thiazide-like diuretic (indapamide) in genetically heterogeneous subgroups of patients with hypertension (HTN) for assessing the prospects of using genetic testing for choosing the antihypertensive treatment regimen.Material and methods. Forty-one patients with grade 1-2 HTN with insufficient effectiveness of previous antihypertensive therapy and 20 healthy individuals were examined to compare the prevalence of gene polymorphism in the Rostov Oblast. Patients with HTN underwent standard diagnostic tests, as well as a molecular genetic test to determine the most clinically significant polymorphic genes involved in the pathogenesis of HTN.Results. A relationship was found between the clinical and morphofunctional characteristics of HTN in patients with polymorphisms of AGT, AGTR2, CYP11B2, GNB3, and NOS3 -786 genes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of the angiotensin-converting enzyme. The effectiveness of using a combination of renin-angiotensin-aldosterone system inhibitor agent with a thiazide-like diuretic as an initial antihypertensive therapy was evaluated.An analysis showed that fixed-dose combination of perindopril (10,0) and indapamide (2,5) (Noliprel A Bi-forte) in genetically heterogeneous subgroups of HTN patients displays a more pronounced antihypertensive and organ-protective effects in individuals with the mutant allele 704C of AGT T704C polymorphism. A significant decrease in blood pressure was demonstrated according to standard 24-hour monitoring (p

Objective. To determine the clinical and genetic risk factors for the development and progression of carotid vascular remodeling according to the prospective observation after five years in patients with essential arterial hypertension (AH). Material and methods. The repeat clinical and instrumental examination with assessment of concomitant cardiovascular risk factors (obesity, smoking, alcohol consumption, physical activity level, hyperglycemia, hypercholesterolemia, signs of depression) was performed in 78 patients with AH. The ultrasound examination of carotid arteries included evaluation of intima-media complex thickness (IMT) and the presence of atherosclerotic plaques. The polymorphism of the genes of the renin-angiotensin-aldosterone system analyzed by polymerase chain reaction and polymorphism of restriction fragment lengths. Results. Progression of vascular remodeling was observed in 26 patients (33.3%) according to the results of carotid arteries examination after 5 years. Age (r=0.53; p=0.001), degree of AH (r=0.43; p=0.0001), level of office systolic blood pressure (r=0.295; p=0.0090), presence of the mutant C allele polymorphism A1166C of the angiotensin II type 1 receptor gene - AGTR1 (r=0.387; p=0.0001), blood glucose (r=0.30; p=0.010), waist circumference (r=0.258; p=0.023) were associated with an increase IMT common carotid artery (CCA) in patients with AH. The multiple linear regression analysis identified independent factors influencing on the IMT CCA - age (b=0.62; p=0.01), males (b=0.321; p=0.01) and the mutant C allele carrier polymorphism A1166C of AGTR1 gene (b=0.312; p=0.01). Conclusions. The progression of carotid vascular remodeling risk factors in patients with AH were age, male gender and polymorphism of A1166C gene AGTR1.

Atrial fibrillation is the most prevalent arrhythmia, and tends to progress. Any structural changes in the heart may lead to its progressive remodelling with increased deposition of connective tissue and fibrosis. Predominance of collagen types I and III synthesis over its degradation leads to accumulation of fibers and to fibrosis. Increase of atrial fibrosis is usually found on autopsy and biopsy. There is relation revealed, of atrial fibrosis grade and postsurgery atrial fibrillation. The mechanisms participating in the structural remodelling and progression of atrial fibrosis are not studied well enough, but there is known role of renin-angiotensinaldosterone system, transforming growth factor, inflammation and matrix metalloproteases. As an alternative, one should consider non-invasive diagnostic methods: magnetic resonance imaging of the heart and biomarkers level measurement. Hyperactivation of the renin-angiotensin-aldosterone system facilitates structural remodelling of the heart and progression of atrial fibrosis. Hyperexpression of the transforming growth factor leads to selective atrial fibrosis, heterogeneity of excitation conduction and fibrillation onset. Matrix metalloproteases are the marker of extracellular degradation. Study of fibrosis biomarkers makes it to increase significantly the efficacy of atrial fibrillation course prediction.

Aim. To analyze relation of blood aldosterone level with comorbidities in patients with chronic heart failure (CHF) with preserved ejection fraction of the left ventricle (EF LV).Material and methods. To the cross-sectional study, 158 patients included: 58 males, 100 females, mean age 62,3±7,4 y. o., with decompensated CHF with preserved EF LV (>50%) and diastolic dysfunction. Patients did not present with primary hyperaldosteronism and did not take mineralocorticoid antagonists within previous 6 weeks. All patients underwent blood specimens collection, and were assessed on the comorbid disorders and conditions. Reference values of the hormone were 40-160 pg/mL.Results. According to the measurements, all patients were selected to two groups: I group included 99 (67,1%) of patients, who had normal hormone level; II — 59 (37,3%) patients with hyperaldosteronemia. Group II patients were younger — 57,75±7,5 y. o. vs 65,02±7,1 y. o. (p10 years) arterial hypertension (AH) — 57,6% vs 25,3% (p

The aim was to study the renin-angiotensin-aldosterone system (RAAS), the level of leptin and kidney function in women with pre-eclampsia (PE) and alimentary obesity (AO).Materials and methods. The levels of renin, angiotensin II, aldoste-rone, leptin, insulin, cortisol, β2-microglobulin, glomerular filtration rate were measured.Results. We show that RAAS, along with a systemic inflammatory response, is a key factor in the development of pre-eclampsia and its progression. The increasing level of leptin has a direct damaging effect on the tubular system of the kidneys.Conclusions. Stimulating the RAAS aggravates the inflammatory response and endothelial dysfunction in women with PE and AO. Elevated concen-trations of leptin in these women have a direct damaging impact on the kidney tubules.

Angiotensin receptor blocker telmisartan is a modern and effective antihypertensive drug which has advantages in comparison with other drugs of the group of angiotensin receptor blockers. Long half-life retains its effect is significant more than 24 hours, which is especially important for blood pressure control in the dangerous morning hours. Telmisartan is excreted by the kidneys less than 2%, making its use safe in patients with renal pathology. High antihypertensive efficacy combined with its excellent tolerability. Telmisartan has the greatest affinity to PPARg-receptors, which is especially important when selecting antihypertensive therapy in patients with arterial hypertension and metabolic disorders, insulin resistance, metabolic disorders. A considerable number of studies showing the effectiveness of treatment with telmisartan in patients with cardiovascular disease, diabetes, metabolic syndrome, nephropathy. The article presents the results of a study of therapeutic equivalence of generic drug is telmisartan, which showed a high bioequivalence to original brand-name formulation and was according to the indications: hypertension and decrease cardiovascular morbidity and mortality in patients aged 55 years and older with a high risk of cardiovascular disease. The results of our observations show comparable antihypertensive efficacy of the original and generic products and well tolerated by the results of questioning of patients.

Angiotensin receptor blocker telmisartan is a modern and effective antihypertensive drug which has advantages in comparison with other drugs of the group of angiotensin receptor blockers. Long half-life retains its effect is significant more than 24 hours, which is especially important for blood pressure control in the dangerous morning hours. Telmisartan is excreted by the kidneys less than 2%, making its use safe in patients with renal pathology. High antihypertensive efficacy combined with its excellent tolerability. Telmisartan has the greatest affinity to PPARg-receptors, which is especially important when selecting antihypertensive therapy in patients with arterial hypertension and metabolic disorders, insulin resistance, metabolic disorders. A considerable number of studies showing the effectiveness of treatment with telmisartan in patients with cardiovascular disease, diabetes, metabolic syndrome, nephropathy. The article presents the results of a study of therapeutic equivalence of generic drug is telmisartan, which showed a high bioequivalence to original brand-name formulation and was according to the indications: hypertension and decrease cardiovascular morbidity and mortality in patients aged 55 years and older with a high risk of cardiovascular disease. The results of our observations show comparable antihypertensive efficacy of the original and generic products and well tolerated by the results of questioning of patients.

Atrial fibrillation (AF) is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS) is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF.

Aim. To analyse the aldosterone level in the blood of patients with different kinds of atrial fibrillation (AF) and sinus rhythm. Material and methods. Totally, 130 patients included (main group) with AF of non-valvular origin. Of those 40 (30,8%) had permanent, 50 (38,4%) — persistent, and 40 (30,8%) — paroxysmal type of atrial fibrillation. The controls consisted of 40 patients with cardiovascular pathology not having anamnesis of AF. Aldosterone levels were measured by immune-enzyme assay. In paroxysmal and persistent AF the measurement was done before returning to sinus rhythm. Reference ranges for aldosterone were 40-160 pg/ml.Results. Aldosterone level in blood was significantly higher in the main group comparing to controls — mean 141,5±41,8 pg/ml vs 105,0±33,1 pg/ml (р

Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

The article reviews the efficacy of angiotensin II receptor blockers in the treatment of hypertension.

The pathogenesis of chronic heart failure (CHF) is a complex multifactorial process, which is a close combination of manifestations of the effects on the cardiovascular system of the etiological factor (s) and the mobilization of a whole complex of compensatory mechanisms [30]. According to the first conceptual models (cardiac (1950s) and cardiorenal (1960s)) pathogenesis, the main role in the formation of CHF belonged to a decrease in cardiac contractility (systolic dysfunction), as well as electrolyte retention and body water. [4, 14, 39]. The aim of the study was to study the role of the renin-angiotensin-aldosterone system and the natriuretic hormone in adaptive changes in water-salt homeostasis with an increase in venous blood return to the heart in healthy and in patients with stable ischemic heart disease with chronic heart failure stage I (stage I). The results of the study concluded: - in healthy individuals, an increase in venous return of blood to the heart (preload) in anti-orthostasis on the background of 0.5% water load is accompanied by adaptive changes in cardiohemodynamics, volemic homeostasis and neurohumoral regulation of water-salt metabolism, manifested by an increased influence of the parasympathetic department ANS, a decrease in heart rate, an increase in ASI while maintaining the IOC at the same level, an increase in diuresis, a decrease in the activity of the RAAS, an increase in the content of α-PNOG; - in patients with coronary artery disease with HNK I st. with an increase in preload at the 30th minute of anti-orthostasis, changes in cardio hemodynamics (decrease in IOC) and cardiac rhythmograms were revealed, indicating a depletion of myocardial reserve capacity and vegetative regulation of heart rhythm. The lack of heart rate dynamics and cardiac rhythmograms in anti-orthostasis reflects an increase in the activity of the sympathetic section of the autonomic nervous system in patients with coronary artery disease with the initial stage of HNK; - kidney reaction to anti-orthostasis and 0.5% water load in patients with coronary artery disease with HNK, I st. expressed in increased diuresis in the absence of changes in the activity of the RAAS, which indicates the predominance of antinatriuretic systems over natriuretic; - the earliest indicator of the development of heart failure in patients with coronary artery disease is sodium retention, aimed at increasing the BCC, venous return of blood to the heart and stimulation of the heterometric mechanism of Frank-Starling.

We observed 140 patients with abdominal obesity (AO) (IDF, 2005), the residents of St. Petersburg (44.6 ± 0.6 years). Metabolic syndrome (MS) (IDF, 2005) was diagnosed in 49.2% of patients with AO. The most frequent component of MS in patients with AO was arterial hypertension (AH). The distribution of genotypes and -alleles of the aldosterone-synthase gene in patients with AO and in the comparison group (56 subjects without AO, 41.0 ± 1.1 years) didn't differ (p> 0.05). Levels of both systolic and diastolic blood pressure (BP) were higher in carriers of -344T allele of aldosterone-synthase gene. Plasma renin activity, plasma aldosterone and glucose levels, anthropometric parameters, serum blood lipids and carbohydrate metabolism indices in obese patients with different genotypes of aldosterone-synthase gene didn't differ. -344T allele of aldosterone-synthase gene in patients with AO is associated with the increased risk of AH.

The renin-angiotensin-aldosterone system (RAAS) activation plays a key role in the chronic kidney disease (CKD) progression and in the cardiovascular complications (CVC) development in patients with diabetes mellitus (DM). RAAS blockers alone are not sufficient to prevent CVC and CVC progression. RAAS upregulation in CKD associated with DM triggers the mineralocorticoid receptors (MCR) hyperactivation which results in fibrosis and inflammation in the heart and kidneys. This review presents the current data about the variety of MCR hyperactivation manifestations, as well as about of multiplicity of MCR hyperactivation ways in DM. The efficacy and safety of finerenone, a new MCR nonsteroidal selective antagonist, are discussed.

Angiotensin-converting enzyme (ACE) inhibitors, a large and heterogeneous group of drugs whose representatives have significant intergroup differences, occupy a special place among many classes of antihypertensive agents. This review focuses on the properties and effects of perindopril, which set off it from other ACE inhibitors, going beyond the scope of the classic effects of this group of drugs.

Arterial hypertension (AH) is one of the basic components of metabolic syndrome that is caused by four factors: autonomic sympathetic dysfunction; activation of the hypothalamic-pituitary-adrenal axis; that of the renin-angiotensin-aldosterone system; and endothelial dysfunction (ED). AH is a slowly progressive hemodynamic disease, the natural course of which is characterized by not only elevated blood pressure (BP), but also by left ventricular hypertrophy, arterial remodeling, and a progressive increase in total peripheral resistance. ED and arterial remodeling play a key role in the pathogenesis of AH in metabolic syndrome. Remodeling of resistant arteries raises peripheral resistance and stabilizes BP and that of large arteries increases their stiffness and a reflected wave, resulting in increased pulse BP, systolic BP, and enhanced left ventricular hypertrophy. Insulin resistance and hyperinsulinemia increase the activity of the renin-angiotensin-aldosterone system and, by enhancing the expression of angiotensinogen, angiotensin II and its type 1 receptors, favors the development of AH, proinflammation, atherosclerosis, and congestive heart failure. Hyperleptinemia, which, by stimulating the activity of the sympathetic nervous system, elevates BP, plays a certain role in the development of AH in metabolic syndrome and obesity.

The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF). It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

Nowadays, obstructive sleep apnea syndrome (OSAS) has been established to promote both structural and functional changes in the kidneys. The basis for these changes is pathophysiological mechanisms, such as hyperproduction of free radicals and disruption of NO-mediated vasodilator responses, activation of the sympathetic autonomic nervous system and the renin-angiotensin-aldosterone system, endothelial dysfunction, development of renal venous hypertension, and stimulation of atrial natriuretic peptide production, which in turn results in increased intraglomerular pressure and glomerular hyperfiltration. In patients with OSAS, the kidneys may be damaged by OSAS-related abnormalities, such as hypertension, diabetes mellitus, metabolic syndrome, erythrocytosis, atherosclerosis, and cor pulmonale, which may also lead to kidney injury under isolated conditions and, when concurrent OSAS is present, may even aggravate the existing kidney injury.

Atrial fibrillation (AF) is one of the most common reasons for decreased life quality and increased mortality rates. Experimental and clinical data show that atrial structural and functional changes contribute to the development and progression of AF. The survey article considers the role of the systemic and local activities of the renin-angiotensin-aldosterone system and inflammatory mediators in the development of atrial structural remodeling, which may be a cause and a consequence of AF.

The review article presents data on the significance of activation of different components of the renin-angiotensin-aldosterone system (RAAS) in metabolic disorder progression and organ damage processes. Based on the analysis of the pharmacological properties of drugs and clinical evidence, the authors discuss the problems of the choice of RAAS blockers. The mechanisms of drug action on metabolic processes, atherogenesis, and vascular damage are discussed.

This review presents the modern views on the effectiveness of water-soluble angiotensin-converting enzyme (ACE) antagonists and calcium antagonists (CA), as monotherapy or as fixed-dose combination therapy, in the treatment of arterial hypertension (AH). The results of the X-ray structural analysis of crystal ACE-lisinopril complexes suggest a highly selective, strong inhibitory effect of lisinopril on various ACE forms of the hormonal renin-angiotensin-aldosterone system and tissue renin-angiotensin systems. The association between specific action mechanisms and therapeutic effects in hypertension is analysed for a third-generation CA amlodipine. The benefits of a fixed-dose combination medication Ekvator (amlodipine 5 mg plus lisinopril 10 mg) in hypertension are described, including its synergetic protective effects.

Aim. To compare the effects of renin-angiotensin-aldosterone system (RAAS) modulators in patients with severe chronic heart failure (CHF). Material and methods. In total, 148 patients (57,4±0,4 years), with severe systolic left ventricular (LV) dysfunction (ejection fraction (EF)

Aim. To study the effectiveness of a direct renin inhibitor, aliskiren, in patients with menopausal metabolic syndrome (MMS), and to assess aliskiren effects on blood pressure (BP), carbohydrate and lipid metabolism parameters, microalbuminuria, and arterial stiffness. Material and methods. The study included 23 women with MMS, to whom aliskiren monotherapy (150-300 mg/d) was administered. At baseline and in the end of the study, anthropometry, carbohydrate and lipid metabolism parameters assessment, 24-hour BP monitoring, and arterial stiffness assessment by volume sphygmography were performed. Results. By the end of the study, most parameters of circadian BP profile significantly decreased. Target levels of systolic and diastolic BP were achieved in 80 % of the patients. There was a significant reduction in postprandial glucose levels. According to the volume sphygmography results, a decrease in arterial stiffness was accompanied by a significant reduction in pulse wave velocity and augmentation index, with normalization of the former parameter. Conclusion. Aliskiren therapy demonstrated not only high antihypertensive effectiveness in MMS patients, but also a reduction in postprandial glucose levels and arterial stiffness.

The object of this study is to evaluate the long-term effects of olmesartan on hypertension and the renin-angiotensinaldosterone system in hypertensive patients. This study evaluated 26 hypertensive male and female outpatients, 38-69 years of age, with a systolic blood pressure ≥160 mm Hg and/or a diastolic blood pressure ≥95 mm Hg. Oral doses of 5 to 40 mg olmesartan were administered once daily. Blood pressure and renin-angiotensin-aldosterone parameters (plasma renin activity and plasma angiotensin I, II, and aldosterone concentrations) were evaluated at 12-16 weeks, 6 months, and 1 year after the start of olmesartan administration. Systolic and diastolic blood pressures were significantly decreased following the administration of olmesartan. The observed decreases in systolic and diastolic blood pressures after 1 year of treatment were 28,8±2,1 mm Hg and 15,8±1,3 mm Hg, respectively. No change was observed in the pulse rate. The plasma renin activity increased significantly from a baseline premedication mean of 1,26±0,31 ng/ml/h to a mean of 2,58±0,74 ng/ml/h and 2,87±0,72 ng/ml/h after 6 months and 1 year of treatment, respectively. Angiotensin II levels decreased significantly from a baseline of 20,4±3,2 pg/ml to a mean of 8,6±2,1 pg/ml and 6,8±1,8 pg/ml after 6 months and 1 year of treatment, respectively. The plasma aldosterone level also decreased significantly after 6 months of treatment. In hypertensive patients, the long-term administration of olmesartan, a novel AT, receptor antagonist, decreased both blood pressure and plasma angiotensin II levels.