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6 Resistin mediates sex-dependent effects of perivascular adipose tissue on vascular function in the shrsp
  1. Sarah McNeilly1,
  2. Heather Y Small1,
  3. Sheon Mary1,2,
  4. Adam Sheikh1,
  5. Christian Delles1
  1. 1BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK
  2. 2Department of Biochemical Sciences, CSIR-National Chemical Laboratory, India

Abstract

Introduction Premenopausal women are relatively protected against hypertension compared to males. Oestrogen levels have been identified as a potential underlying cause, but many of the pathophysiological mechanisms remain to be determined. Altered perivascular adipose tissue (PVAT) function has been identified to have vasoactive effects. However, in hypertension, sex-dependent differences of PVAT have not yet been explored.

Hypothesis Sex-dependent effects of PVAT mediate altered vascular function in hypertension.

Approach and result The effect of PVAT was investigated on resistance vessels of 16 week old male and female stroke-prone spontaneously hypertensive rats (SHRSP). This preclinical model of hypertension presents with a sex-difference in the development of hypertension comparable to humans. Wire-myography was used on 3rd order mesenteric vessels to assess vascular function. Noradrenaline mediated vasoconstriction was increased in SHRSP males compared to females (maximum contraction: male +PVAT 113.3±1.1% vs female +PVAT 91.4%±11.36%). 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%). To explore the cause of sex-dependent differences in PVAT an adipokine array with subsequent western blot validation was carried out. This identified resistin as a potential modifier of vascular reactivity. Resistin was increased by approximately 2-fold in SHRSP male mesenteric PVAT. Further wire-myography experiments with male and female vessels pre-treated 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[40 ng/ml] 36.8%±2.3%).

Conclusion These findings indicate a novel role for resistin in sex-dependent PVAT mediated vascular function in hypertension through a KATP channel mediated mechanism.

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