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

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Abstract

The endothelin-B receptor (ETBR) mediates vasodilation in young women, an effect that is absent in postmenopausal women. We have previously demonstrated that ETBR-mediated vasodilation is regulated by estradiol (E2) in young women; however, the impact of E2 on ETBR function in postmenopausal women remains unknown. Accordingly, the objective of this study was to test the hypothesis that E2 exposure restores ETBR-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 (42̊C) using laser Doppler flowmetry combined with intradermal microdialysis perfusions of lactated Ringer’s (control) and ETBR antagonist (BQ-788, 300 nM) at baseline and after E2 administration. There was no effect of E2 on ETBR 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 ETBR function in postmenopausal women.

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Nuckols, V. R., Shoemaker, L. N., Kuczmarski, A. V., Haigh, K. M., McGinty, S. J., Del Vecchio, A. R., … Wenner, M. M. (2025). Short-term estradiol administration does not restore endothelin-B receptor-mediated vasodilation in postmenopausal women. American Journal of Physiology - Heart and Circulatory Physiology, 328(2), H327–H332. https://doi.org/10.1152/ajpheart.00815.2024

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