[Functional state of the mesenteric arteries with higt fat intake in rats with streptozotocin-induced diabetes].

An increase in the incidence of diabetes mellitus (DM) is associated with excessive consumption of fats and carbohydrates, while DM leads to the development of cardiovascular diseases. The aim of the research was to evaluate the effect of a high-fat diet (HFD) on the functional state of the mesenteric arteries in vivo in Wistar rats with DM. Material and methods. The study was conducted on 45 male Wistar rats with an initial body weight of 220-240 g, which were divided into 3 equal groups. Animals of the control group received a standard diet for 3 months. Rats of the second group (STZ) were fed a standard diet, after 8 weeks the animals were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg body weight). Animals in the STZ+HFD group received HFD (50% beef tallow), and an injection of STZ (35 mg/kg). We assessed the effect of HFD on endothelium-dependent and endothelium-free reactions of phenylephrine (PE) precontracted mesenteric arteries under the action of agonists in the absence and use of blockers of NO-synthase (L-NAME), cyclooxygenase (indomethacin), and K+-channels (tetraethylammonium), using microphoto- and videorecording of vessel diameter in vivo. Results. DM in rats led to an increase in the constrictor reaction to FE; in animals of the STZ+HFD group, the diameter of the vessel decreased by 63.7±4.7%; in the STZ group, by 60.4±3.8%; and in the control group, by 48.9±4.1%. HFD and DM induction had no effect on the amount of relaxation under the action of sodium nitroprusside. The amplitude of acetylcholine-induced relaxation of the mesenteric arteries of rats with DM in the absence of blockers was significantly lower (by 27.1% on average in the STZ+HFD group, by 14.6% in the STZ group) compared with control animals. After NO synthase inhibition, the relaxation amplitude decreased in the STZ+HFD group by 48.6±3.2%, in the STZ group by 56.1±2.8%, and in control animals by 58.3±3.1% compared with the dilatation amplitude without the use of a blocker. Acetylcholine-induced vascular dilatation under conditions of simultaneous use of a complex of three blockers - L-NAME, indomethacin and tetraethylammonium was reduced in rats with DM treated with HFD by an average of 18.9% and in animals of the STZ group by 22.1% compared with control animals. Conclusion. Thus, excessive fat intake in rats with STZ-induced DM enhances the impairment of the functional state of the mesenteric arteries compared to animals with DM that received a standard diet. In HFD in rats with DM, a decrease in endotheliumdependent vasodilation was mediated as a failure of NO-dependent relaxation mechanisms and a decrease in the efficiency of the mechanism of endothelial hyperpolarization, whereas in rats with DM fed a standard diet, it was predominantly a disturbance in the mechanism of endothelial hyperpolarization.

[Postgenomic and structural changes in the myocardia of Wistar rats fed a high-salt diet].

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

[Urinary miRNA expression in cynomolgus macaques (Macaca fascicularis) fed high salt rations].

High food intake of sodium chloride is associated with damage not only the cardiovascular system, but also the kidneys. The mechanisms of the potential negative effects of high-salt diets on the kidneys have not been established. The aim of the study was to trace the changes in relative expression of miRNA-21, 203 and 133 in urine of cynomolgus macaques (Macaca fascicularis) fed high-salt diet with and without isolated soy proteins. Material and methods. The object of the study was 18 male cynomolgus macaques (Macaca fascicularis) aged 6-8 years with a body weight of 5.1-9.7 kg. The animals were divided in 3 groups (6 individuals each). The animals of the first (control) group received a standard diet (2 g NaCl/kg feed). The animals of the second group were fed high-salt diet (8 g NaCl/kg feed), of the third - high-salt diet combined with SUPRO 760 isolated soy protein (200 g/kg feed; instead of milk and egg proteins, corn gluten). Access to water was free. The follow-up period in this study was 4 months. In animals blood pressure (BP) and relative level of microRNA (miRNA) expression in urine were measured. Results and discussion. Keeping monkeys on the studied diets for 4 months did not lead to significant changes in systolic or diastolic BP compared with the initial level. In the control group, there were no distinct changes in the expression of miRNA-21 in urine during observation. In the other two groups, there was a significant increase (approximately equally) of this parameter in comparison with the initial values. Both high-salt diets resulted in a significant increase in the relative level of expression of miRNA-133 and miRNA-203 in urine compared to basal values. However, the increase in these parameters 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. Conclusion. Possible, potentially negative effects of high-salt diets on kidney may be mediated by epigenomic mechanisms and partially modulated by the inclusion of isolated soy proteins in the diet.