Abstract 931: Compensatory Response of Perivascular Adipose Tissue to Vascular Dysfunction in Metabolic Syndrome Rats Involves Apelin

Abstract

Perivascular adipose tissue (PVAT) regulates vascular homeostasis including vascular tone via release of adipokines. Using SHRSP.Z- Lepr fa /IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS), we have demonstrated that mesenteric PVAT enhances vasodilation under impaired vasodilation, in response to nitric oxide. We have also shown that the compensatory effect of PVAT disappears later in the course of MetS. Apelin is an adipokine that is produced at high levels in obesity and acts as a vasorelaxing factor. In this study, we evaluated the role of apelin in the enhancing effect of mesenteric PVAT on relaxations in SHRSP.ZF rats, by examining whether apelin canenhance vasorelaxation in the mesenteric arteries of SHRSP.ZF rats without PVAT, as it does in those with PVAT. Furthermore, we investigated whether apelin expression changes with increasing age. SHRSP.ZF rats at 17, 20, 23, and 30 weeks old were used. The mesenteric artery and surrounding adipose tissue were isolated from each rat; PVAT samples were isolated from surrounding adipose tissue; and the mRNA transcript level of apelin was examined by quantitative real-time PCR assays. Mesenteric arterial ring preparations with and without PVAT were made, and after a stable contraction was obtained by adding phenylephrine, relaxation was elicited using acetylcholine in the presence or absence of apelin (100 ng/mL, 20 min). There was no significant difference in apelin mRNA levels between 17 and 20 weeks, but there was a decrease at 23 and 30 weeks of age, which was when the enhancing effect of PVAT on vasodilation in SHRSP.ZF rats was impaired. In the presence of apelin, acetylcholine-induced relaxation in arteries without PVAT was significantly increased to the level of the response in arteries with PVAT in SHRSP.ZF rats at 20 weeks. These findings suggest that apelin is involved in the enhancing effect of PVAT in MetS rat mesenteric artery, and decreases in the level is associated with deterioration of PVAT function. Further study to investigate the mechanisms underlying the decrease in apelin production with increasing age in metabolic syndrome is needed, butthe apelin level could be one of the predictors for development of cardiovascular complications in patients with MetS.