Short-term estradiol administration does not restore endothelin-B receptor-mediated vasodilation in postmenopausal women

Abstract

The endothelin-B receptor (ET_BR) mediates vasodilation in young women, an effect that is absent in postmenopausal women. We have previously demonstrated that ET_BR-mediated vasodilation is regulated by estradiol (E₂) in young women; however, the impact of E₂ on ET_BR function in postmenopausal women remains unknown. Accordingly, the objective of this study was to test the hypothesis that E₂ exposure restores ET_BR-mediated dilation in postmenopausal women. Ten healthy postmenopausal women (55 ± 2 yr of age, 5 ± 3 years since menopause) completed the study. E₂ was administered by transdermal patch for 7 days (0.1 mg/day, Vivelle-Dot patch). Vasodilation in the cutaneous microcirculation (microvascular endothelial function) was measured via local heating (42°C) using laser Doppler flowmetry combined with intradermal microdialysis perfusions of lactated Ringer's (control) and ET_BR antagonist (BQ-788, 300 nM) at baseline and after E₂ administration. There was no effect of E₂ on ET_BR function [hormone × site, F(1,9) = 0.77, P = 0.40]. These data demonstrate that in contrast to findings in premenopausal women, E₂ administration does not restore ET_BR function in postmenopausal women.NEW & NOTEWORTHY The vascular endothelial endothelin-B receptor (ET_BR) mediates vasodilation in premenopausal women, an effect modulated by estradiol. ET_BR-mediated vasodilation is lost in postmenopausal women, but the effect of exogenous estradiol administration on ET_BR function in postmenopausal women is not known. During estradiol administration, ET_BR blockade did not affect cutaneous microvascular vasodilatory response to local heating. We demonstrate that exogenous estradiol administration does not restore ET_BR-mediated vasodilation in postmenopausal women.

Keywords: endothelial function; endothelin; estrogen; menopause; skin blood flow.

Figure 1:

Cutaneous vascular conductance expressed as a percent of maximal vasodilation (%CVC_max) during local heating and perfusion of lactated Ringer’s (control) and ET_BR blockade (BQ-788) at baseline (grey bar) and with estradiol (E₂) administration (white bar). Data are results of two-way within-group ANOVA (hormone by site) presented as means (bars) with individual values. Labels are mean±SD.