Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.