Abstract 4358798: Renal artery relaxation and its modulation by perivascular adipose tissue in relation to kidney function

Abstract

Metabolic syndrome (MetS) is a cluster of conditions that increases the risk of cardiovascular diseases and type 2 diabetes. Perivascular adipose tissue (PVAT) regulates arterial tone. We previously demonstrated that renal arterial PVAT enhances vasorelaxation responses in rats with MetS and hypertension and that PVAT dysfunction contributes to the development of kidney disease, resulting from increase in renal arterial tone. The question arises as to whether high blood pressure plays a role in PVAT and/or kidney dysfunction in MetS. Therefore, we investigated the relationship between modulation by renal arterial PVAT and kidney function in rats with MetS but without hypertension. Renal arteries were isolated from fa/fa and +/+ (lean) male rats of the Zucker fatty (ZF) strain and from fa/fa and fa/+ (lean) male rats of the ZF diabetes mellitus (ZFDM) strain at 20 weeks of age. Systolic blood pressure (sBP) was measured using the tail-cuff method. Serum insulin and glucose levels, as well as urinary protein and glucose, were measured using commercial kits and UROPAPER III ‘Eiken’. Vasorelaxation in response to sodium nitroprusside was examined in arteries with (+) and without (-) PVAT using the organ bath method. There were no significant differences in sBP among the four groups, and rats were normotensive. In the ZFDM strain, serum glucose levels were higher in fa/fa rats than in heterozygous rats, while in the ZF strain, serum insulin levels were higher in fa/fa rats than in heterozygous rats. Urinary glucose was detected only in fa/fa ZFDM rats, and urinary protein levels were elevated in fa/fa rats compared to those in lean rats in both strains. Relaxation of the renal arteries without PVAT was reduced only in fa/fa rats of the ZF strain. In contrast, PVAT attenuated relaxation only in fa/fa rats of the ZFDM strain. These findings suggest that reduced vasorelaxation in fa/fa ZF rats, which have insulin resistance, and the release of vasocontractile factor(s) from renal arterial PVAT in fa/fa ZFDM rats, which have low serum insulin levels in DM, may decrease renal blood flow, contributing to kidney dysfunction.