Abstract P504: Resistin Mediates Sex-dependent Effects of Perivascular Adipose Tissue on Vascular Function in the SHRSP

Abstract

Background: Premenopausal women are relatively protected against hypertension compared to males. Estrogen levels have been identified as a potential underlying cause, but the pathophysiological mechanisms remain incompletely understood. We hypothesised that sex-dependent effects of perivascular adipose tissuePVAT mediate altered vascular function in hypertension. Methods: The effect of PVAT was investigated on resistance vessels of 16 week old male and female stroke-prone spontaneously hypertensive rats (SHRSP). Results: Wire myography was used on 3 rd -order mesenteric vessels (maximum contraction: male +PVAT 113.3±1.1 vs. female +PVAT 91.4±11.36 %). Noradrenaline mediated vasoconstriction was increased in SHRSP males compared to females. K ATP channel-mediated vasorelaxation by cromakalim was impaired in males compared to females (maximum relaxation: male +PVAT 46.9±3.9 % vs. female +PVAT 97.3±2.7 %) A cross-over study assessing function of male PVAT on female vessels and vice versa confirmed the reduced K ATP mediated vasorelaxation induced by male PVAT (maximum relaxation: female +PVAT female 90.6±1.4 % vs. female +PVAT male 65.8±3.5 %). An adipokine array with subsequent western blot validation identified resistin as a potential modifier of vascular reactivity. Resistin was increased by approximately 2-fold in SHRSP male PVAT. Male and female vessels pretreated with resistin (40ng/ml) showed no difference in response to noradrenaline. However, vasorelaxation in response to cromakalim was significantly impaired in resistin treated female vessels, similar to levels observed in male vessels (maximum relaxation: female +PVAT 97.3±0.9 % vs. female +PVAT +resistin 36.8 ±2.3 %). Conclusion: We identified a novel role for resistin in sex-dependent PVAT mediated vascular function in hypertension through a K ATP channel mediated mechanism.