Objective. The purpose of the work is to use a meta-analysis to investigate the effect of melatonin monotherapy on the hemodynamic parameters of normotensive and hypertensive rats.

Design and methods. For our metaanalysis, we selected 39 publications, of which 28 studied the effect of melatonin monotherapy on hemodynamic parameters in normotensive rats, 12 in SHR rats, 7 in rats with fructose-induced hypertension, 3 in rats with L-NAME-induced hypertension. Meta-analysis of study results was conducted using the statistical program Review Manager 5.3 (Cochrane Library).

Results. Our meta-analysis showed that melatonin has a dose-dependent hypotensive and bradycardic effect with a single intravenous administration. The hypotensive effect of chronic administration of melatonin will increase with the duration of therapy. Moreover, the hypotensive effect of melatonin is significantly higher in hypertensive animals compared to normotensive ones. Long-term therapy with melatonin reduced blood pressure levels in normotensive animals by no more than 2 mm Hg, and in hypertensive rats by an average of 20–30 mm Hg.

Conclusions. As a result, since melatonin demonstrates a good hypotensive effect in various models of experimental hypertension, it is advisable to continue clinical studies of the possibility of using melatonin in the treatment of hypertension, which should focus on monotherapy, dose selection, various methods of increasing bioavailability and prolonging the effect.

The intestinal microbiota not only mediates the influence of a number of risk factors for cardiovascular diseases on the body, but can also play an active role in the regulation of blood pressure (BP) by changing the permeability of the intestinal epithelial barrier and the production of vasoactive metabolites. At the same time, the study of the molecular mechanisms underlying the influence of intestinal microbiota on BP levels is at an early stage. The review analyzes the scientific literature on the role of intestinal microbiota in the development of arterial hypertension (HTN), describes the key mechanisms of the prohypertensive action of intestinal microbiota metabolites, and presents data on new approaches to the treatment of HTN based on effects on the composition and function of intestinal microflora. BP levels are affected by molecules whose concentration in the blood is directly or indirectly related to the activity of intestinal microflora. These bioactive molecules can be divided into two groups — those formed by cells of the human immune system as a result of stimulation by the microbiota and those formed enzymatically as a result of the metabolic activity of the microbiota itself. The first group includes molecular mechanisms associated with immune activation and systemic inflammatory response, and the second group includes short-chain fatty acids, trimethylamine-N-oxide, bile acids, uremic toxins and biogenic amines. HTN is accompanied by specific changes in the composition of the intestinal microbiota, and in recent years, researchers have established cause-and-effect relationships between certain enterotypes and the development of HTN. Moreover, established HTN itself causes changes in the intestinal microbiome profile. A deeper understanding of the molecular mechanisms mediating the influence of microbiota on BP may serve as the basis for the development of new approaches to the treatment of HTN.

Long-term responders for calcium channel blocker (CCB) therapy represent the minority population among the patients with idiopathic/hereditary/drug-induced pulmonary arterial hypertension (PAH). The frequency of vasoreactive testing (VRT) has been dramatically decreased over the past decade in clinical practice, while the amount of PAH specific therapy prescription has been raised substantially. Current review highlights the frequency of VRT in the modern population of patients with idiopathic PAH. Interconnections between pulmonary vascular morphology, physiology and genetics in long-term responders for CCB therapy and patients with negative VRT are analyzed. Pulmonary vasoreactive reserve prognostic value discussed.

Objective. To conduct a prospective (2-year) comparative analysis of the dynamics of 24-hour ambulatory blood pressure monitoring (ABPM) in patients with arterial hypertension (HTN) and previous COVID-19 infection working in the conditions of the Arctic watch.

Design and methods. In the Medical Unit of Gazprom Dobycha Yamburg LLC (GDY) in the polar shift settlement of Yamburg, 347 patients were examined: 222 men (M) and 125 women (W). All of them underwent ABPM according to the standard protocol in 2019 and 2022. Among them, 261 patients had confirmed COVID-19 between 2020 and 2021 and were treated in the Medical Unit of GDY. Among the examined M and W, according to medical history in 2019, 80 % of M (178 from 222 people) and 66 % of W (82 from 125 people) had elevated blood pressure (BP), p = 0,003. Among patients with HTN, 109 M (61,2 %) and 42 W (51,2 %) survived after COVID-19, p = 0,129. They formed observation group (n = 151). Comparison group included HTN patients without COVID-19 (n = 109).

Results. In patients with HTN who had COVID-19, ABPM showed an increase in average daily systolic BP (SBP) values after 2 years: from 134,5 (12,3) to 140,5 (11,8) mmHg (p < 0,0001) and diastolic BP (DBP): from 96,6 (14,0) to 105,1 (13,4) mmHg (p < 0,0001), hypertensive load time indices (TI): TI SBP24 (from 49,5 (29,3) to 61,6 (28,1) mmHg (p < 0,0001) and TI DBP24 from 69,3 (30,5) to 83,4 (21,9) mmHg (p < 0,0001), increase in daytime SBP variability (p = 0,048), decrease in daily SBP indices by 1,2 %: from 7,9 (4,6) to 6,7 (4,3) (p = 0,038) and DBP by 2,0 %: from 9,7 (4,8) to 7,7 (4,7) (p = 0,032). Desynchronization of SBP and DBP rhythms were found by chronobiological analysis.

Conclusions. A prospective comparative analysis of the dynamics of ABPM in patients with HTN after COVID-19 in the conditions of the Arctic watch showed an increase in the average daily values of SBP and DBP and their daily variability, deterioration in the daily BP profile with an increase in the “night peaker” phenotype. In patients with HTN who did not have COVID-19, a prospective analysis of ABPM showed a significant increase in DBP and average daily hypertensive load of DBP, which may contribute to further cardiovascular remodeling. In patients with HTN who have recovered from COVID-19, desynchronization processes of SBP and DBP rhythms intensify, which requires an in-depth analysis of the chronobiological structure of the rhythm BP.

Objective. To identify the effectiveness of sacubitril/valsartan versus valsartan in reducing blood pressure (BP) in patients with arterial hypertension (HTN) 1–2 degree.

Design and methods. The study included 105 patients, among them 90 were included in the effectiveness analysis and were observed for 12 months in an outpatient setting. In accordance with the protocol, 90 patients completed the study, 44 of them received sacubitril/ valsartan (97/103 mg), 46 received valsartan (160 mg). The dynamics of clinical BP in mm Hg and rates of achieving target BP levels in treatment groups were assessed.

Results. Systolic after 12 months decreased more significantly in sacubitril/valsartan group versus valsartan: by 14,68 ± 9,33 vs 6,17 ± 4,81 mmHg (p = 0,007). The rate of achieving target BP was higher in the sacubitril/valsartan group (61,41 % vs 34,8 %, p < 0,01).

Conclusions. Among patients with 1–2 degree HTN, sacubitril/valsartan reduced blood pressure to a greater extent than valsartan alone and was not inferior to the latter in terms of safety criteria.

Objective. To study possible correlations between the quantitative characteristics of fat depots in the abdominal and perirenal regions according to magnetic resonance imaging (MRI) data with metabolic and immunoinflammatory parameters, renal function, blood pressure (BP), as well as anthropometric data in patients with resistant hypertension (RH).

Design and methods. Sixty-three patients (26 men) with RH aged 60 [54; 64] years who were receiving individual treatment with antihypertensive medication (mean, 4,3 ± 1,1 drug per day) were included in the study. Systolic/diastolic/pulse BP (SBP/DBP/PBP) was 157,7 ± 15,4 / 86,3 ± 13,6 / 71,3 ± 14,5 mm Hg. Mean body mass index (BMI) 34,1 [31,0; 38,5] kg/m², waist circumference (WC) 108 [102; 113] cm (95,2 % with abdominal obesity). Diabetes mellitus type 2 suffered 51,6 %, chronic kidney disease C3–30,6 %. Clinical and laboratory examinations were performed. Creatinine level with estimated glomerular filtration rate (CKD-EPI), biomarker levels were assessed by ELISA. MRI was performed in a high-field tomograph with a magnetic field induction on 1,5 T. Mean parameter values in apparently healthy volunteers were considered normal. The area of visceral adipose tissue (S VAT) and subcutaneous adipose tissue (S SAT) was determined at the L4-L5 level (normal 123,5 [101,0; 169,0] and 216,5 [167,0; 287,0] cm², respectively); kidney diameter — the anterior-posterior size of the kidney at the level of the renal vein (normal 5,0 [4,4; 5,4] cm); the thickness of perirenal adipose tissue (PRAT) as the difference between the distance between the sheets of Gerota’s fascia at the level of the renal vein and the diameter of the kidney (normal 1,2 [0,9; 2,4] cm); thickness of anterior subcutaneous adipose tissue (SATT) at the level of the umbilicus (normal 2,7 [1,8; 3,8] cm), the ratio of PRAT/SATT (normal 0,72 ± 0,61).

Results. An increase was observed in all fat depots: S VAT 271,2 ± 104,4 cm², S SAT 309,5 [236,0; 400,0] cm², PRAT 2,7 [1,8; 3,9] cm, SATT 3,0 [2,3; 3,7] cm. Anthropometric parameters were associated with S VAT and S SAT. The thickness of PRAT correlated only with weight (r = 0,44) and WC (r = 0,41), whereas SATT correlated with BMI (r = 0,49). The PRAT/SATT ratio was not dependent on BMI. S VAT was associated with the level of PBP (r = 0,30). The following associations were observed with metainflammatory markers: TNF-α with S VAT (r = 0,31) and S SAT (r = 0,43) and with BMI (r = 0,32) and WC (r = 0,38); hsCRP with S SAT (r = 0,30), PRAT thickness (r = 0,34), and SATT (r = 0,34); leptin level correlated only with subcutaneous adipose tissue (S SAT, r = 0,60 and SATT, r = 0,69) and BMI (r = 0,51). Kidney size was 5,5 [5,0; 6,0] cm and was not associated with BMI. A decrease in kidney size was associated with a decrease in estimated glomerular filtration rate (r = 0,36). Glomerular filtration rate was associated with PRAT, as was creatinine (r = 0,43), which was also correlated with S VAT (r = 0,32). No correlations were found between renal function and anthropometric data.

Conclusions. In patients with RH, there is an increase in the size of fat depots in the abdominal and perirenal regions according to MRI, which are closely related to anthropometric parameters and markers of inflammation. A direct correlation between the serum concentration of leptin and the size of subcutaneous adipose tissue has been established. An increase in the ratio of PRAT/SATT indicates an increase in the predominantly visceral component of adipose tissue and is associated with an increase in PBP, which reflects vascular stiffness. The decrease in the filtration function of the kidneys is correlated with an increase in the size of perirenal fat depots in the absence of direct links with dimensions of subcutaneous adipose tissue and anthropometric characteristics. 

Due to its broad spectrum of pathogenic target points, fixed-dose combination therapy is considered a benchmark approach to successful treatment of arterial hypertension (HTN) and HTN-associated cardiovascular conditions. This results from endothelium insufficiency of various origin, so the use of combination of angiotensinconverting enzyme inhibitors and calcium channel blockers is an optimal treatment choice. The review highlights key points of single pill amlodipine and perindopril A combination use and its key position in modern concept of hypertension management. We have focused on the metabolic neutrality of fixed-dose amlodipine and perindopril A combination, its ability to delay rapid progression of already acquired metabolic changes. We briefly highlight fundamental observational and randomized studies, in particular, those regarding effectiveness of the drug components and its effect on the end points as a fixed-dose combination. The last but not least, we emphasize vasoand cardioprotective properties of the drug as well as its safety profile.