Abstract 604: Influence of Perivascular Adipose Tissue on Vasodilation in Metabolic Syndrome

Abstract

Metabolic syndrome facilitates the development of cardiovascular disease due to atherosclerosis. We propose that chronic oxidative-nitrative stress is linked to the development of vascular dysfunction in response to nitric oxide (NO) in the coronary and mesenteric arteries of SHRSP.Z- Lepr fa /IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome. Perivascular adipose tissue (PVAT), which is located outside blood vessels, has now been recognized as playing a role in vascular function. We assessed the role of PVAT in vascular dysfunction observed in SHRSP.ZF rats with metabolic syndrome. We used SHRSP.ZF rats at 13, 18, and 23 weeks, and observed obesity, hyperlipidemia, glucose intolerance, and hypertension from 13 weeks until 23 weeks of age. Relaxation induced by acetylcholine and sodium nitroprusside were unchanged in isolated mesenteric arteries of SHRSP.ZF rats at 13 weeks of age, but were impaired at 18 and 23 weeks of age compared to those in control Wistar-Kyoto rats (WKY). The relaxation induced by both agonists was greater in the mesenteric arteries enveloped by PVAT than in those without PVAT in SHRSP.ZF rats at 18 and 23 weeks of age. The relaxation in the arteries with PVAT in SHRSP.ZF rats were at similar levels as those in the arteries without PVAT in age-matched WKY. In contrast, no difference was observed in the relaxation levels in the arteries with and without PVAT in SHRSP.ZF rats at 13 weeks of age and in WKY at all ages. Histological analysis of PVAT showed that adipocytes in PVAT of SHRSP.ZF rats at 20 weeks of age were larger than those observed in WKY. Impaired NO-dependent vasodilation was also observed in aortas of SHRSP.ZF rats at 23 weeks of age compared to that in age-matched WKY, but the relaxation was not altered by the presence of PVAT. SHRSP.ZF rats with metabolic syndrome showed impairment in the NO-dependent pathway in resistant arteries, with increasing age/exposure to metabolic abnormalities. PVAT may help in the regulation of vasodilation to compensate for the impaired vasodilation observed under pathophysiological conditions, such as metabolic syndrome.