Changes in microRNA expression in the urine and endotelium-dependent regulation of vassel tone in Wistar rats received a high-salt diet

Abstract

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.