Endothelin‐B Receptor Responses in Young and Postmenopausal Women

Abstract

Cardiovascular disease (CVD) is the leading cause of the death in women, and postmenopausal women (PMW) are at an increased risk for developing CVD. Endothelin‐1 (ET‐1) contributes to age‐related endothelial dysfunction in men via the ETA receptor. However, there are sex differences in ET‐1 regulation of vascular function, and ETB receptors are influenced by fluctuations in ovarian hormones.PURPOSEThe purpose of this study was to test the hypothesis that ETB receptors contribute to impaired microvascular function in PMW.METHODSWe measured skin blood flow (SkBF) in 11 young women (YW; 22±1 years, 22±1 kg/m2) and 10 PMW (58±2 years, 24±1 kg/m2) using laser Doppler flowmetry during microdialysis perfusions of lactated Ringer's (control), an ETB receptor antagonist (BQ‐788, 300nM), and an ETA receptor antagonist (BQ‐123, 500 nM). We utilized local skin heating (42°C) to induce microvascular vasodilation, followed by perfusion of sodium nitroprusside (28mM) to elicit maximal dilation. Mean arterial blood pressure (MAP) was measured throughout. Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP during the plateau established during local heating, and expressed as a percent of maximal dilation. Unpaired t‐tests were used to compare variables between YW and PMW.RESULTSResting MAP was higher in PMW (93±2 mmHg) compared to YW (80±2 mmHg; P<0.05). Vasodilatory responses to local heating (control site) tended to be lower in PMW (YW: 91±2 vs. PMW: 81±5 CVC % max; P=0.12). ETB receptor blockade tended to decrease cutaneous vasodilation in YW (control: 91±2 vs. BQ‐788: 85±3 CVC % max; P=0.08), but tended to enhanced vasodilation in PMW (control: 81±5 vs. BQ‐788: 92±1 CVC % max; P=0.08). ETA receptor blockade had minimal effect in YW (control: 91±2 vs. BQ‐123: 92±2 CVC % max; P=0.35), but tended to increase cutaneous vasodilation in PMW (control: 81±5 vs. BQ‐123: 90±2 CVC % max; P=0.11).CONCLUSIONETB receptors appear to mediate vasodilation in YW. However, microvascular vasodilation is blunted in PMW, possibly due to greater ETB and ETA mediated vasoconstriction.Support or Funding InformationSupported by NIH Grant U54 GM 104941 01A1 and University of Delaware Research Foundation.