4.2 SEX-DEPENDENT EFFECTS OF PERIVASCULAR ADIPOSE TISSUE ON VASCULAR FUNCTION

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 tissue PVAT 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 3rd-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. KATP 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 KATP mediated vasorelaxation induced by male PVAT (maximum relaxation: female +PVATfemale 90.6 ± 1.4 % vs. female +PVATmale 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 (40 ng/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 KATP channel mediated mechanism.