The aim: to evaluate functional and structural changes in blood vessels and myocardium in Wistar rats at different stages of the formation of experimental kidney dysfunction.Materials and Methods. Four groups of animals were studied. The first two groups consisted of rats subjected to 5/6 nephrectomy (NE). The period after NE is 2 or 4 months. The third and fourth groups included sham-operated (SO) animals of a similar observation period. After the end of the experiment, blood pressure was measured in rats, the left ventricular mass index (LVMI) was calculated, a biochemical blood test, histological, immunohistochemical and electron microscopic examination of the myocardium were performed, and the contractile activity of the portal vein was recorded for a period of 2 months (in vitro).Results. 2 months after NE, an increase in blood pressure, LVMI, and a decrease in the autorhythmic contractile activity of the portal vein were detected in rats. At the histological level, thickening of cardiomyocytes and arterial vessel walls and the presence of perivascular fibrosis were noted. After 4 months, in rats with NE, the increase in blood pressure, cardiomyocyte hypertrophy and perivascular fibrosis progressed. The thickness of cardiomyocytes was 14.1±3.11 μm, which was significantly greater than in the group with NE for 2 months (12.5±1.5 μm; p=0.008). At this period of observation, electron microscopic examination revealed deintegration of myofibrils, disruption of myofibril stacking and z-disk structure, and changes in the shape of mitochondria. 2 months after NE, an increase in the area of open capillaries was detected in rats (1902.8±202.9 μm²) compared to the corresponding LO animals (730.4±58.2 μm²; p=0.000). As renal dysfunction develops, the capillary area tends to increase (2139.1±396.5 μm²; p =0.120).Conclusion. In Wistar rats with renal dysfunction, changes were detected not only in the level of blood pressure, but also in the functional activity of the intravenous fluid, as well as in the structural components of the myocardium – cardiomyocytes, stroma and blood vessels. The increase in myocardial mass at the histological level was manifested by a significant increase in the thickness of cardiomyocytes, the volume of connective tissue, and the thickness of the wall of arterial vessels, reaching a maximum value at a longer period after NE.

BACKGROUND. Dietary adjustment is an important point in the treatment of chronic kidney disease (CKD). However, at present, the effect of a diet with a high NaCl content on the state of the cardiovascular system in patients with early stages of CKD has not been sufficiently studied. The AIM: to evaluate blood pressure levels and changes in the myocardium of Wistar rats with early stage renal dysfunction fed a high-salt diet for a long time. MATERIALS AND METHODS: The study was performed on male Wistar rats. The control group consisted of sham-operated animals (LO-group), receiving a standard diet (0.34 % NaCl), the second – rats subjected to resection of ¾ of the kidney parenchyma, receiving a standard diet (NE-group), the third – rats, subjected to ¾ NE, receiving high sodium diet (4 % NaCl, NE+HSD). After 4 months, the rats were assessed for blood pressure (BP), levels of urea, creatinine, sodium in the blood serum, daily diuresis, albumin content in the urine, myocardial mass index (IMM) and left ventricular myocardial mass index (IMLV), and a histological examination of the myocardium was performed. RESULTS: In rats with kidney dysfunction, an increase in blood pressure was detected, most pronounced in the NE+HSD group. In rats of this group, albumin excretion, connective tissue volume, arterial diameter, thickness of the adventitia and media of myocardial vessels increased relative to the indicators of rats with NE receiving a standard diet. IMLV in NE+HSD rats was higher by 16.4 %, and IMM by 10.9 % than in animals with NE on a standard diet. The groups with NE did not differ from each other in the content of urea and creatinine in the blood serum, although these indicators were higher than in LO animals. There were no differences between groups in serum sodium levels. CONCLUSION: Prolonged consumption of a diet with a high content of table salt contributes to the development of the initial stages of CKD in Wistar rats, promotes blood pressure growth and myocardial remodeling, manifested primarily in the progression of cardiomyocyte hypertrophy and myocardial fibrosis.

The renin-angiotensin-aldosterone system (RAAS) is involved in the regulation of kidney function and blood pressure (BP). In renal dysfunction, hyperactivation of the RAAS leads to an increase in BP and impaired permeability of the nephron glomerular filter. Blockade of the RAAS is one of the methods of nephroprotection. Objective. To compare the effect of an angiotensin-converting enzyme inhibitor (IACE), angiotensin I receptor blocker (ARB), and a selective slow calcium channel blocker (BCC) on the functional state of the microvasculature of the skin of rats with nephrectomy (NE), fed with a high-salt diet (HS). Design and methods. Five groups of Wistar rats were studied. The SO group: sham-operated animals that received a standard diet; the HS+NE group: rats with ¾ NE and HS (4 % NaCl); HS+NE+Ler-, HS+NE+Lis-, HS+NE+Los-groups: rats with ¾ NE and HS, that were treated with the BCC lerkanidipin (Ler, 3 mg/kg), IACE lisinopril (Lis, 30 mg/kg) or the ARB losartan (Los, 10 mg/kg), respectively. After 4 months, a study was performed using laser Doppler flowmetry (LDF). Results. In rats of the HS+NE group, uremia is accompanied by an increase in BP (by 16,9 % compared to the SO group). The treatment with IACE and ARB in rats with NE and HS prevents the rise in BP, while BCC does not reduce BP. The LDF-study showed that the increased intensity of initial skin perfusion in rats of the HS+NE group (7,2 ± 0,3 compared to 6,5 ± 0,2 p. u. in the SO group) is not corrected by BCC (6,9 ± 0,3 p. u.), but is reduced by the use of IACE (6,4 ± 0,2 p. u.) and ARB (6,1 ± 0,2 p. u.). Wavelet analysis showed that the increase in tonic effects on blood vessels in the endothelial, neurogenic and myogenic regulatory circuits, characteristic of renal dysfunction, decreases with the use of all studied drugs. RAAS blockade in rats with ¾ NE and HS does not prevent a decrease in the reactivity of skin microvessels to acetylcholine (ACh), and the use of BCC restores the response of skin blood flow to ACh to the control level. Conclusions. In Wistar rats, NE in combination with HS leads to an increase in BP, an increase in tonic effects on skin microvessels in the endothelial, neurogenic and myogenic ranges, as well as a decrease in the reactivity of skin blood flow to ACh. Inhibition of the RAAS by the treatment of IACE and ARB prevents the increase in BP, but does not improve the reactivity of skin microvessels. The use of BCC in rats with NE and HS does not reduce BP, but improves the reactivity of skin microvasculature to ACh.

Background. Cardiovascular complications are common in chronic kidney disease (CKD). The relationship between the cardiovascular system and the kidneys is complex and diverse, but the question of the mechanisms of the influence of excess NaCl consumption on the functional state of blood vessels during renal dysfunction remains relevant.The aim: to evaluate the effect of a high-salt diet on the functional state of microcirculatory vessels (MCR) of the skin in rats at an early stage of renal dysfunction.Material and Methods. The study was conducted on Wistar rats. The first SO group included animals subjected to sham surgery (SO) and receiving a standard diet (0.34% NaCl); in the second, HS group – animals that also underwent a sham operation, but received a high-salt diet (4% NaCl); in the third, NE group – rats subjected to ¾ nephrectomy (NE) and receiving a standard diet; the fourth, HS+ NE group included rats subjected to ¾ NE and fed a high-salt diet (4% NaCl). Blood pressure (BP) was measured in the tail using the cuff method (Sistola, Russia), MCR was assessed using laser Doppler flowmetry (LDF). The reactivity of skin microvessels was assessed by changes in the MCR index before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (NP). Based on the assessment of the spectral characteristics of fluctuations in the MCR index obtained using Wavelet analysis, the value of endothelial, neurogenic and myogenic microvascular tone was calculated.Results. 4 months after ¾ NE, rats showed a decrease in the excretory function of the kidneys. In rats on a highsalt diet, an increase in blood urea levels was noted. The blood pressure in rats of the SO+HS group did not significantly differ from the control animals of the SO group (131 ± 8 and 125 ± 4 mmHg, respectively, NS), NE led to a significant increase in blood pressure (135 ± 5 mmHg in rats of the NE group, and 145 ± 7 mmHg – in the NE+HS group). The average MCR was higher in rats receiving a high-salt diet (SO+HS and NE+HS groups), compared with animals of the corresponding group receiving a standard diet. The combination of NE and high-salt load has an inhibitory effect on the amplitude of fluctuations in the intensity of perfusion in all studied ranges: endothelial, neurogenic and myogenic, while the calculated value of skin microvascular tone in three ranges was the highest in NE+HS group rats. In all experimental groups, the reactivity to AH was reduced compared with the SO group, and after NP iontophoresis, the average perfusion rate significantly decreased only in groups of animals receiving a high-salt diet: SO+HS and NE+HS.Conclusion. A high-salt diet in rats with an initial stage of renal dysfunction contributes to an increase in blood pressure and a decrease in natriuresis compared with animals with NE who received a standard diet. With excessive consumption of table salt in rats after NE, the intensity of cutaneous MCR increases, while reducing the variability of the MCR index. A high-salt diet in rats with NE modifies the characteristics of the spectral components of fluctuations in the MCR index, indicating an increase in tonic effects on skin microvessels in the endothelial, neurogenic and myogenic ranges. With hypernatrial load, animals with ¾ NE have a decrease in the reactivity of cutaneous microvessels to AH and NP, which is mediated by both a decrease in endothelial NO production and a decrease in MMC sensitivity to NO.

Excessive salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Given the cardioprotective effect of soy proteins in chronic kidney disease, the question arose of the possibility of leveling dietary interventions, in particular soy proteins, the damaging effect of a high-salt diet on the cardiovascular system. The aim of this work is to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling and skin histomorphology in monkeys. The study was performed on male Javan macaques (Macaca fascicularis). The control group received a standard diet (2 g NaCl/kg feed). The second was a high-salt diet (8 g NaCl/kg feed), the third was a high-salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography, registration of BP and heart rate were performed at baseline, after 4 and 12 months. After 12 months, a histological examination of the musculocutaneous flap was performed. In all animals, BP and heart rate did not change significantly during 12 months. In macaques on a high-salt diet, by the end of the study, deterioration in systolic and diastolic functions of the left ventricle (LV) was noted. In animals receiving additional soy protein, these changes leveled out. After 12 months, macaques fed soy protein had LV myocardial mass smaller and higher LV contractility than animals fed excess salt without soy protein. In monkeys on a high-salt diet, accumulation of collagen fibers in the hypodermis, hyalinization of the cytoplasm of capillary smooth muscle cells, perivascular and perineural edema of the reticular dermis were revealed. In animals treated with soy protein, skin capillary remodeling was less pronounced. Thus, high salt intake leads to adverse structural and functional disorders of the heart and blood vessels in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

BACKGROUND. Modeling of chronic kidney disease using nephrectomy of 5/6 kidney parenchyma is actively used in experimental nephrology. However, the remaining 17 % of the organ parenchyma is associated with severe renal fibrosis in humans. A high-salt diet has traditionally been considered as a systemic hemodynamic model for the development of chronic kidney disease.THE AIM: to compare the functional disorders that occur in rats with nephrectomy of ¾ of the kidneys and when using only a high-salt diet.MATERIAL AND METHODS. The study was performed on 30 male Wistar rats. The animals were randomly divided into 3 equal groups: control (falsely operated, L), high-salt diet (falsely operated, LVD), nephrectomy ¾ renal parenchyma (NE). The rats received a balanced laboratory feed daily, differing only in the content of sodium chloride (NaCl). In the L and NE groups, rats received a feed containing 0.34 % NaCl, and in the VD group – 4 % NaCl. The duration of follow-up was 16 weeks. Systolic blood pressure (SBP) was measured on the tail by the cuff method. The serum and urine concentrations of creatinine, urea, potassium, sodium, chlorine, as well as the degree of proteinuria and albuminuria were determined.RESULTS. During the observation, the SBP in group L did not change. In the LVD group, SBP increased from 120 [120; 125] mmHg to 130.0 [125.0; 140.0] mmHg, p=0.011. In the NE group, SBP also increased from 120 [120; 125] mmHg to 135.0 [132.5; 137.5] mmHg, p=0.011. In the LVD group, there was an increase in serum creatinine concentration compared to the control to 52.5 [50.0; 56.0] mmol/l, p=0.0001; urea to 6.0 [5.6; 6.6] mmol/l, p=0.0001; potassium to 5.6 [5.3; 5.8] mmol/l, p=0.0001; chlorine up to 87.5 [86.6; 87.9] mmol/l, p= 0.0001. At the same time, creatinine clearance decreased from 187.5 [160.0; 205.0] ml/min in the L group to 92.0 [81.2; 99.0] ml/min, p=0.0003 in the LVD group and to 83.9 [65.7; 85.9] ml/min p=0.0001 in the NE group. The value of albuminuria before the end of the experiment was statistically significantly higher compared to the control in both the LVD group of 12.12 [6.36;18.41] mg/g creatinine, p= 0.0001, and in the NE group of 72.5 [61.6; 92.9] mg/g creatinine, p= 0.0001. When conducting a nonparametric correlation analysis (all three observation groups were combined), a statistically significant relationship was noted between the level of SBP after 1 month from the start of the experiment and the amount of albuminuria at its completion (Rs=0.583 p=0.001). A statistically significant relationship between the value of SBP and creatinine clearance was revealed before the end of the experiment (Rs=-0.700 p=0.005). Also, before the end of the experiment, a statistically significant relationship between albuminuria and creatinine clearance was revealed (Rs=-0.671 p=0.006).CONCLUSION. The NE model of the renal parenchyma is expected to be accompanied by the development of less severe functional changes compared to NE 5/6 of the renal parenchyma. In this regard, we assume that its use may be useful in studying the effectiveness of nephroprotective measures at the initial stages of CKD development. The negative effects of a high-salt diet are comparable in a number of indicators to nephrectomy of the renal parenchyma. Traditionally, an increase in salt intake is associated with an increase in blood pressure, which could result in an increase in albuminuria. However, we could not identify any relationships between albuminuria and the value of SAD. We assume that the model of a high-salt diet can be considered as a variant of a local, rather than a systemic hemodynamic model of the development of chronic kidney disease. In the future, we will present the results of nephrobiopsy in the experimental groups described above.

THE AIM: to evaluate the effect of a high-salt diet on the level of miRNA expression in urine and the mechanisms of endothelium-dependent vascular dilatation in rats. MATERIALS AND METHODS: 20 Wistar rats were divided into two equal groups. The high salt (HS) group received 8 % NaCl in the diet, the control (NS) received the standard diet (0.34 % NaCl). After 4 months, blood pressure (BP), left ventricular mass index (IMLV) were assessed in rats, and relative expression levels of miRNA-21, miRNA-133, and miRNA-203 were determined in urine. The reactivity of the rings of the aorta and the superior mesenteric artery (SMA) to acetylcholine (ACh) was assessed in vitro in isometric mode. RESULTS: there was no significant difference between the groups in terms of mean blood pressure (p> 0.05). However, in HS-rats an increase in IMLV was noted. The relative levels of expression of miRNA-21, miRNA-133, and miRNA-203 in the urine of rats fed a high-salt diet increased significantly as compared to the values of control animals. A high-salt diet resulted in a decrease in the reactivity of vascular segments precontracted with phenylephrine to ACh. A high-salt diet resulted in a decrease in the reactivity of vascular segments precontracted with phenylephrine to ACh. In the HS-group, the decrease in the amplitude of vasodilation under the action of ACh under conditions of blockade of NO-synthase (with the use of L-NIO) was less compared to the reaction in the absence of the blocker, than the NS-group: in the SMA of the HS group – by 45 %, NS group – by 69.4 %, in the aorta HS-group – by 49.4 %, NS-group – by 80.7 %. In contrast to the aorta, blockade of Ca2+-sensitive K+-channels in SMA (under the conditions of administration of tetraethylammonium, TRAM-34, or apamin) weakened ACh-induced relaxation, and in HS-rats, the decrease in vasodilation was more pronounced. CONCLUSION: consumption of a high-salt diet, without changing blood pressure, increases IMLV and the level of miRNA expression in the urine, and also reduces endothelium-dependent vascular relaxation, mediated, in particular, by impaired endothelial NO production, which is more pronounced in the aorta than in the SMA.

THE AIM: to evaluate the effect of low protein diet supplemented with ketosteril on morphological and epigenomic changes in the myocardium of Wistar rats with simulated kidney dysfunction . MATERIALS AND METHODS. The work was performed on male Wistar rats subjected to 5/6 nephrectomy (NE). The first group after NE received a standard diet (20.16% animal protein ), the second – low protein diet (LPD), including 10% ketosteril . Control rats received a standard diet . After 4 months , blood pressure (BP) and left ventricular mass index (LVMI) were assessed in rats , and a histological examination of the myocardium was performed . In the myocardium , the relative expression levels of NF- kB , miRNA-21, miRNA-133, and miRNA-203 were determined . RESULTS. After 4 months in rats with NE on a standard diet , an increase in blood pressure , an increase in the mass index of the LV myocardium was recorded . MBD with the inclusion of 10% Ketosteril slowed down the growth of systolic blood pressure and the development of LV myocardial hypertrophy in rats with kidney dysfunction . At the histological level , the use of LPD provided a decrease in the degree of hypertrophy of cardiomyocytes and degenerative changes in cardiomyocytes . Animals treated with LPD had less pronounced diffuse and perivascular fibrosis compared with animals fed normal food . The use of MBD slowed down the increase in the relative level of expression of the NFκB gene and miRNA-21 in the myocardium of rats with NE and promoted an increase in the expression level of miRNA-133 and miRNA-203 compared to the indices of animals with NE that received standard food . CONCLUSION: long-term use of LPD with the use of ketoanalogues of essential amino acids can have a potential cardioprotective effect in CKD, slowing down the growth of blood pressure , an increase in LV myocardial mass and the formation of structural changes in the myocardium . It is possible that a decrease in the expression of NF- kB and miRNA-21, as well as an increase in the expression of miRNA-203 and 133 in the myocardium , can play a significant role in this .

INTRODUCTION. A high intake of sodium chloride from food is associated with damage not only to the cardiovascular system but also to the kidneys. The mechanisms of the negative effects of high-salt diets on the kidneys have not been established. One of the important links in this process can be microRNAs, which can modulate gene expression at the post-transcriptional level. It is also not known whether soy proteins can counter the kidney remodeling associated with increased salt intake.THE AIM. To estimate the expression levels of miRNA-133 and 203 in blood serum and urine and miRNA-21 in the urine of cynomolgus macaques received diets for a long time with various table salt contents, including and not including soy proteins.MATERIALS AND METHODS. Three groups (6 individuals in each) of male cynomolgus macaques at the age of 6–8 years were studied. The first group (control) received a standard diet, the second – a diet with a high content of table salt (8 g NaCl / kg feed), the third – a diet with high salt content in combination with SUPRO 760 soy protein (200 g protein/kg feed). Blood pressure was measured in animals 12 months later. In monkey urine, the relative expression levels of miRNA-21, miRNA-133, and miRNA-203 were determined, in blood serum – the expression levels of miRNA-133 and miRNA-203.RESULTS. During the follow-up period in the control group, there were no significant changes in the studied parameters. In the groups that received high-salt diets throughout the year, blood pressure also did not change significantly. There was no change in the level of expression of miRNA-133 in the blood serum of monkeys fed a high-salt diet and a standard protein diet. However, in macaques fed a diet high in salt in combination with soy protein, the serum expression of this miRNA was significantly reduced. The expression of miRNA-203 in blood serum did not change significantly. In the control group, there were no changes in the expression of miRNA-21 in urine. In the other two samples, this parameter increased in comparison with the initial values. Both high-salt diets resulted in a significant increase in the relative level of miRNA-133 expression in urine compared to basal values. However, the increase in this indicator in the group of animals fed a high-salt diet in combination with soy isolate was significantly less than in monkeys fed only a high-salt diet. Expression of miRNA-203 in urine was significantly increased only in the group with a high content of table salt without added soy protein.CONCLUSIONS. It is possible that the effects of high-salt diets on the kidney may be mediated by epigenomic mechanisms and partially modulated by the inclusion of isolated soy proteins in the diet.

INTRODUCTION. Magnesium is the second most common intracellular cation, is a cofactor for more than 300 enzymes, affects the functional state of the cardiovascular system through various mechanisms, in particular, through the action on the smooth muscle cells of the vessels, modulation of the renin-angiotensin-aldosterone system, regulation of sodium and calcium homeostasis. Therefore, maintaining a normal level of magnesium in the blood is an urgent task, and the consumption of drinking water enriched with magnesium can be considered as a method of correcting an insufficient intake of exogenous magnesium.THE AIM. The purpose of the study was determined – to evaluate the effect of drinking water with different contents of magnesium ions and a complex of magnesium with calcium on the state of the cardiovascular system of rats with genetically determined arterial hypertension. MATERIALS AND METHODS. From 6–7 weeks of age, male SHR rats received drinking water of various compositions for two months: in the first group (hCа+Mg) – with increased content of calcium and magnesium (120 mg/l Ca2+ and 45 mg/l Mg2+), the second (nCа+Mg) – drinking water normalized by mineral composition (60 mg/l Ca2+ and 25 mg/l Mg2+), in the third (hMg) – enriched Mg2+ (45 mg/l), the fourth (control) control group – St. Petersburg tap water with a low mineral content (8 mg/l Ca2+ and 3 mg/l Mg2+). WKY rats were divided into 2 groups: one group (hMg) received water enriched with Mg2+ (45 mg/l), the control WKY (control) group received water with a low mineral content (8 mg/l Ca2+ and 3 mg/l Mg2+). After 2 months, the blood pressure of rats on the tail was measured by the cuff method, the level of urea, cholesterol, total calcium, and albumin in the blood serum was analyzed, left ventricular mass index (LVMI) and myocardial mass index (MMI) were calculated. The spontaneous contractile activity of the portal vein (PV) was recorded by myography (in vitro) in isometric mode. The following were analyzed: frequency, total and maximum amplitude of phase-tonic contractions, the area under the contraction curve in 1 min, which characterizes the work performed by the vein. %). RESULTS. Enrichment of drinking water with Ca2+ and Mg2+ had a more pronounced antihypertensive effect in SHR rats compared with the hMg2+ group. In WKY rats, magnesium enrichment of water did not affect blood pressure. Modification of the mineral composition of drinking water did not affect MMI and LVMI in both SHR and WKY rats. Interlinear differences were found in the contractile activity of PV in control rats (the amplitude of PV contractions in SHR rats was greater than WKY. Consumption of water enriched with minerals decreased the amplitude of PV contractions, the largest decrease was in the hMg2+ group (in SHR, 2.6 times, in WKY, 1.5 times as compared to the control of the corresponding line). The value of the work performed by the PV in the control SHR rats was greater than in the control rats of the WKY line, and the enrichment of water with magnesium caused a decrease in the work performed by the PV only in rats SHR lines (by 55.6 %), but not for WKY. CONCLUSIONS. In rats, the consumption of drinking water enriched only with magnesium has an antihypertensive effect; however, it suppresses the spontaneous contractile activity of PV. It is advisable to use a complex of magnesium with calcium, which lowers blood pressure, but maintains an adequate level of contractile activity of the PV.

INTRODUCTION . Beta-catenin is a structural protein of adhering junction and intercalated discs of cardiomyocytes as well as the main intracellular messenger of the canonical WNT (cWNT) signaling pathway. The dysregulation of the cWNT signaling and the rearrangement of the cardiomyocyte cytoskeleton accompany the cardiovascular disorders in chronic kidney disease (CKD). THE AIM : to investigate the expression and distribution of β-catenin, calcineurin A, and TGF-β1 in the myocardium of spontaneously hypertensive rats (SHR) with CKD, sham operated SHR and Wistar Kyoto rats of the corresponding age. MATERIAL AND METHODS . Systolic blood pressure (BP), heart rate (HR), myocardial mass index (MMI), creatinine concentration (Cr), myocardial beta-catenin expression and renal Klotho expression, morphological light-optical study of kidney and myocardium tissues was performed in sham operated (SO) Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and SHR with 5/6 nephrectomy (Nx). RESULTS . SHR rats showed higher values of BP, MMI, cardiomyocyte diameter, myocardial fibrosis area, and lower Klotho levels compared to WKY rats. Nx SHR had lower kidney function and renal Klotho expression, higher BP and MMI compared to SHR. An increase in the cardiomyocytes diameter and the area of myocardial fibrosis was accompanied by the overexpression of β-catenin, calcineurin A, and TGF-β1 in the myocardium. CONCLUSION . The upregulation of canonical Wnt signaling and cellular programs of cardiomyocyte hypertrophy mediated by Klotho deficiency can be involved in myocardial remodeling in chronic renal dysfunction.

Uromodulin (UMO) is a multifunctional glycoprotein expressed in the epithelial cells of the thick ascending part of the loop of Henle. Currently a lot of data about mechanisms of biosynthesis, apical and basolateral transport of UMO, changes in urine and blood concentrations in different kidney compartments damage, roles of UMO in protecting kidneys from infections, maintaining mineral homeostasis, development of arterial hypertension and the participation of this glycoprotein in other physiological and pathological processes has been accumulated. The article discusses the clinical significance of UMO in the development and progression of chronic kidney disease, prognostic value of UMO urine and blood concentrations in terms of the risk of cardiovascular diseases and probability of acute kidney damage in patients with cardiovascular pathology. Briefly highlights issues of UMO gene mutation and development of autosomal dominant tubulointerstitial kidney disease.

INTRODUCTION . High dietary sodium chloride intake has traditionally been considered an important factor in cardiovascular risk and an increase in blood pressure (BP). However, much remains unclear about the relationship between dietary sodium and cardiovascular health. In particular, it was shown that in rats a high content of salt in the diet can lead to miocardial remodeling/damage without increasing BP. It is possible whether this phenomenon in primates remains unknown. The AIM of the study was to trace the dynamics of BP and some echocardiographic (EchoCG) parameters in cynomolgus macaques ( Macaca fascicularis ), which have been on a high sodium chloride diet for a long time. MATERIAL AND METHODS . 12 male cynomolgus macaques 6-8 years with a body weight of 5,15-9,7 kg were studied. The animals were divided into two groups (six individuals each). The first (control) received a standard diet, the second – a diet high in sodium chloride (8 g NaCl/kg feed). After four and fourteen months, in the animals were measured blood pressure and conducted echocardiographic examination (EchoCG). RESULTS . During the follow-up period in the control group, no significant changes in the studied parameters were recorded. Increased salt intake at four months resulted in a significant decrease in left ventricular end-systolic dimension and an increase in ejection fraction values. After fourteen months, both of these indices returned, practically, to the initial level, but there was a significant increase in the thickness of the posterior wall of the left ventricle in systole and a decrease in systolic excursion of the tricuspid valve annulus compared with the basal data. BP in the salt group also did not change significantly. CONCLUSION . Cynomolgus macaques are able to resist an increase in blood pressure induced by a long stay on a high-salt diet, but in primates under such conditions, the initial manifestations of functional and structural rearrangement of the heart can be observed.

The work is dedicated to the 170th anniversary of the outstanding physiologist I.P. Pavlova. Reflected some points of his scientific activities and biographies. Particular attention is paid to the image of I.P. Pavlova in the works of Russian artists and sculptors – contemporaries of the scientist.

Background. Even a moderate decrease in glomerular filtration rate leads to an increased risk of cardiovascular diseases (CVD), which is the leading cause of mortality in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) underlies CVD development in renal dysfunction. The prevalence of LVH in patients with CKD stages 2–4 is 50–70 % and reaches 95 % at the beginning of dialysis, which significantly exceeds the number of cases in general population (15–21 %). Common hemodynamic factors associated with chronic kidney damage —hypertension (HTN), activation of the renin-angiotensin system, anemia, fluid and sodium retention, and others largely explain the high prevalence of LVH among patients with CKD. Nevertheless, the existence of additional non-hemodynamic mechanisms of myocardial remodeling (MR) is evident.Objective. To investigate the associations between the MR physiological/histological characteristics and laboratory parameters of calcium-phosphate metabolism in the initial stages of experimental CKD. Design and methods. Four groups of spontaneously hypertensive rats (SHR) were studied (n = 35): 3/4 nephrectomized rats (Nx) one month exposed after surgery (Nx(1), n = 9), 5/6 Nx two months after surgery (Nx(2), n = 8), sham operated rats one month after surgery (SO(1), n = 9) and two months after surgery (SO(2), n = 9). Myocardial mass index (MMI), systolic blood pressure (BP), proteinuria, creatinine (Cr) concentration, total calcium (Ca) and inorganic phosphate (Pi), 25-OH vitamin D (25OHD) and parathyroid hormone (PTH) in serum, myocardial morphology were studied in all experimental animals.Results. The models corresponded to the 1–3 stages CKD. There were no significant changes in serum total Ca (p = 0,066), Pi (p = 0,051) and PTH (p = 0,015) concentrations, the level of 25OHD was significantly lower in Nx(2) rats vs control (p = 0,015). MMI increased in all nephrectomized rats (p = 0,008). The cardiomyocytes (CM) thickness increased in Nx(1) and Nx(2) animals compared to the corresponding controls (p = 0,010, p = 0,002). A significant increase in interstitial (IF) and perivascular (PF) fibrosis occurred in Nx(2) rats with more damaging influence (p = 0,017, p = 0,004). CM thickness, IF and PF increased with the elevation of BP (r = 0,39, p = 0,038, r = 0,47, p = 0,026, r = 0,49, p = 0,031) and serum Cr (r = 0,68, p = 0,001, r = 0,61, p = 0,003, r = 0,69, p = 0,001), and the decrease in serum 25OHD concentration (r = –0,045, p = 0,047, r = –0,50, p = 0,020, r = –0,52, p = 0,012). Multiple linear regression analysis showed, that 25OHD is an independent predictor of myocardial fibrosis (IF: β = –0,38 ± 0,18, p = 0,047, PF: β = –0,34 ± 0,15, p = 0,032).Conclusions. The initial stages of CKD accompanied with HTN are associated with serum 25OHD concentration decrease CM hypertrophy and myocardial fibrosis. The CM growth is an earlier event in relation to the interstitial fibrosis. The obtained data suggest a possible role of vitamin D deficiency in the development of myocardial fibrotic lesions.

BACKGROUND. Klotho is a transmembrane and circulating protein primarily synthesized by the kidney. Klotho deficiency characterizes chronic kidney disease (CKD), as myocardial hypertrophy (GM). The cardioprotective effect of the Klotho protein is due to the negative regulation of a variety of stress signals, leading to the activation of the hypertrophic intracellular signaling pathway calcineurin (CaN) / NFAT in the myocardium. The effect of Klotho may presumably be mediated by the modulation of Ca2 + channels and / or Foxo factors essential for CaN signaling. THE AIM: to study the activity of CaN/ NFAT signaling pathway in the myocardium and to determine the molecular mechanisms of its regulation in conditions of Klotho level decrease in spontaneous hypertensive rats (SHR) with experimental CKD. MATERIAL AND METHODS. The experimental model of CKD was 3/4 or 5/6 nephrectomy (Nx) in SHR. Sham-operated (SO) SHR, and Wistar Kyoto rats (WKY) were used as controls. In all animals were measured systolic blood pressure, myocardial mass index – MMI, creatinine clearance, cardiomyocyte (CM) diameter, Klotho levels in serum (ELISA) and kidney (IHC), myocardial expression of calcineurin (IHC, PCR), transcription factor NFAT (IHC), TRPC6 (IHC), FOXO3A (PCR) and phosphor-Foxo1/3/4 (IHC). The tissue expressions of calcineurin, TRPC6, and Klotho were calculated as the IHC specific product area to the field of view ratio. NFAT expression was evaluated as the positively stained nuclei to the number of nuclei ratio in the field of view. Measurements were performed in 10 fields of view for each histology slide. RESULTS. The model has corresponded to the initial stages of CKD. The increase in MMI (p = 0.005) and CM diameter (p = 0.002) were observed compared in Nx rats to SO. Renal Klotho expression (p < 0.001), and serum Klotho level (p = 0.019) were lower in the Nx. In multiple linear regression analyzes, the values of MMI and CM thickness were independently associated with the level of renal Klotho protein (β = -0.38 ± 0.16, p = 0.026, β = -0.64 ± 0.14, p <0.001, respectively). Nx and systemic hypertension were accompanied by an increase in the expression of the calcineurin gene (p = 0.005) and cytoplasmic calcineurin in CM (p = 0.004), the number of NFAT-positive nuclei (p = 0.007), and an increase in the expression of the FOXO3A gene (p <0.001) in the absence of accumulation of phosphorylated Foxo1/3/4 in CM cytoplasm. SHR rats were characterized by positive IHC staining for TRPC6 compared to WKY (p = 0.004). The expression of calcineurin and TRPC6 varied co-directionally (r = 0.69, p <0.001), and both of these indicators were associated with the Klotho levels (calcineurin vs Klotho in the kidney, r = -0.73, p <0.001; TRPC6 vs Klotho in serum, r = -0.43, p = 0.025). CONCLUSION. The development of Klotho deficiency on early-stage CKD is associated with the expression of transient Ca2+ channels TRPC6 and activation of the calcineurin / NFAT hypertrophic signaling pathway in cardiomyocytes.

The aim : to evaluate changes in endothelium-dependent regulation of the tone of blood vessels (aorta and superior mesenteric artery) in rats 4 months after the removal of 5/6 renal tissue. Material and methods. An experimental CKD model was created by resection of 5/6 mass of renal tissue. The experimental group included animals (n = 12), subjected to nephrectomy (NE). The control group consisted of sham-operated (SO) rats (n = 10). Researches of vascular reactivity were performed on ring segments 2 mm long, which were excised from the aorta and superior mesenteric artery (SMA). A total of 23 segments of the aorta and 17 segments of SMA from rats after NE and 18 segments of the aorta and 15 segments of SMA from control animals were prepared. To measure the strength of contractions of the drugs, a FORT-10 sensor (WPI, USA) was used. The effects of acetylcholine (Ach, 1 x10 -6 M) on blood vessels, previously exposed to phenylephrine (1 x10 -5 M), and the response of vessels to Ach under conditions of prior exposure to TEA (1 x 10 -3 mol / l) and L-NAME (1 x10 -4 mol / l) were evaluated. Results. NE for a period of 4 months led to arterial hypertension - BP in the NE group of rats was higher (165, 0 ± 9.8 mm Hg) compared with SO (127.2 ± 9.7 mm Hg, р <0,001), and to myocardial remodeling (LVMI in NE rat was 2.72 ± 0.11 mg / g compared to 2.35 ± 0.09 mg / in the SO group, р <0,001 ). NE led to a decrease in dilatation of aortic and BWA fragments on the ACh compared with LO animals. Under the conditions of NO blocking, the NO synthase inhibitor — L-NAME — also had a lower response to ACh in rats with NE. The preliminary blockade of the Ca2 + -activated K + channels of high conductivity with the introduction of TEA resulted in a decrease in vasodilation caused by ACh in NE rat compared with the SO group. Conclusion. Resection of 5/6 of the kidney tissue mass in rats causes a decrease in vascular reactivity on the ACh. Endothelial dysfunction of rats after NE is associated with impairment of both NO-related and hyperpolarization-dependent endothelial cells in pathways of the vascular tone regulation.

BACKGROUND. Increased salt intake is associated with a number of cardiovascular events, including increased blood pressure (BP) and the development of left ventricular hypertrophy (LVH). However, there is much evidence that a high content of sodium chloride in the diet does not always lead to an increase in BP, but almost inevitably causes cardiac remodeling, in particular, LVH. Many aspects of myocardial remodeling induced by high sodium content in the food have not been studied enough. THE AIM of the study was to trace the echocardiographic changes in Wistar rats fed the high salt ration and the high salt ration supplemented with soy proteins.MATERIAL AND METHODS. Echocardiography and BP measurements were performed on male Wistar rats, divided into three groups. The first (control; n = 8) included rats that received standard laboratory feed (20.16 % animal protein and 0.34 % NaCl); the second (n = 10) – animals that received standard feed and 8 % NaCl (high salt ration). The third group (n = 10) consisted of rats who consumed a low-protein diet containing 10 % soy protein isolate (SUPRO 760) and 8 % NaCl. The follow-up period was 2 and 4 months.THE RESULTS of the study showed that: (1) the intake of a large amount of salt with a diet does not necessarily lead to the formation of arterial hypertension; (2) despite the absence of a distinct increase in BP, under these conditions signs of cardiac remodeling, in particular, LVH, appear rather quickly; (3) supplementing a high-salt diet with soy isolates counteracts the development of LVH.CONCLUSION. High salt intake with food can cause heart remodeling, regardless of blood pressure, while soy proteins can counteract this process.

Background and objective.Currently, the role of miRNA‑21 in the development of heart and kidney damage and their interaction remains unclear. Therefore, the aim of this work is to assess the impact of changes in the expression of microRNA‑21 in myocardial tissue in the development of cardiac remodeling with chronic reduction in the mass of active nephrons in the experiment.Design and methods.Wistar drain rats were divided into two groups. The first (control) group included nine falsely operated animals. The second (n = 9) group included rats with step-by-step resection of 5/6 renal tissue. After 4 months after surgery, blood pressure (BP) was measured, heart ultrasound (echocardiography, EchoCG) was performed and the level of relative expression of microRNA‑21 in myocardial tissue was determined.Results. The rats with an experimental decrease in the mass of functioning nephrons, showed significantly higher levels of BP, microRNA‑21 expression in the myocardium and the thickness of the interventricular septum (according to EchoCG). They also demonstrated smaller end-systolic dimension of the left ventricle and systolic motion of the mitral valve ring.Conclusions. Our data indicate the potential role of miRNA‑21 in the development of concentric left ventricular remodeling while reducing the number of functioning nephrons. This remodeling is characterized by the prevalence of myocardial hypertrophy over fibrosis. However, the specific mechanisms linking microRNA in the pathogenesis of heart remodeling require further research.

Background and objective. Currently, the role of miRNA‑21 in the development of heart and kidney damage and their interaction remains unclear. Therefore, the aim of this work is to assess the impact of changes in the expression of microRNA‑21 in myocardial tissue in the development of cardiac remodeling with chronic reduction in the mass of active nephrons in the experiment. Design and methods. Wistar drain rats were divided into two groups. The first (control) group included nine falsely operated animals. The second (n = 9) group included rats with step-by-step resection of 5/6 renal tissue. After 4 months after surgery, blood pressure (BP) was measured, heart ultrasound (echocardiography, EchoCG) was performed and the level of relative expression of microRNA‑21 in myocardial tissue was determined. Results . The rats with an experimental decrease in the mass of functioning nephrons, showed significantly higher levels of BP, microRNA‑21 expression in the myocardium and the thickness of the interventricular septum (according to EchoCG). They also demonstrated smaller end-systolic dimension of the left ventricle and systolic motion of the mitral valve ring. Conclusions . Our data indicate the potential role of miRNA‑21 in the development of concentric left ventricular remodeling while reducing the number of functioning nephrons. This remodeling is characterized by the prevalence of myocardial hypertrophy over fibrosis. However, the specific mechanisms linking microRNA in the pathogenesis of heart remodeling require further research.