Vasomotor Function and Its Modulation by Perivascular Adipose Tissue Vary Depending on Metabolic Syndrome Stage

BACKGROUND: Perivascular adipose tissue (PVAT), found outside blood vessels, enhances vasorelaxation when endothelium-mediated vasorelaxation fails, as observed in the mesenteric arteries of rats with metabolic syndrome (MetS) and hypertension; however, whether high blood pressure contributes to PVAT dysfunction remains unclear. We, therefore, aimed to investigate vascular function and PVAT modulation in the mesenteric arteries of rats with MetS but no hypertension. METHODS: Mesenteric arteries were isolated from both lean and obese male Zucker fatty (ZF) and ZF diabetes mellitus (ZFDM) rats at 20 and 30 weeks of age. Vasorelaxation was examined in arteries with or without PVAT; mRNA levels in PVAT and arteries were examined using the organ bath method and quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: Sodium nitroprusside-induced relaxations were lower in the obese versus lean ZF rats, and PVAT increased them to levels comparable to those in lean rats at 20 weeks. These enhancements disappeared after 30 weeks. The mRNA expression of apelin in PVAT and its receptor was upregulated in the arteries of obese rats, and its levels correlated positively with the enhancing effect of PVAT. In obese ZFDM rats, PVAT attenuated relaxation at both 20 and 30 weeks. Levels of chemerin mRNA expression in PVAT were higher in ZFDM versus ZF rats; however, treatment with chemerin or a chemerin receptor antagonist did not alter vasorelaxation in ZFDM rats. CONCLUSIONS: Apelin may contribute to compensatory PVAT modulation during vascular dysfunction in obese ZF rats. PVAT inhibits vasorelaxation by releasing a contractile factor other than chemerin in ZFDM rats. Thus, it may modulate vascular tone differently depending on MetS stage.