ET B receptor-mediated vasodilation is regulated by estradiol in young women

The endothelin-B (ET ) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ET receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E ) on ET receptor function in...

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Published in:American journal of physiology. Heart and circulatory physiology 2021-09, Vol.321 (3), p.H592-H598
Main Authors: Shoemaker, Leena N, Haigh, Katherine M, Kuczmarski, Andrew V, McGinty, Shane J, Welti, Laura M, Hobson, Joshua C, Edwards, David G, Feinberg, Ronald F, Wenner, Megan M
Format: Article
Language:English
Subjects:
Adult
Endothelin B Receptor Antagonists - pharmacology
Estradiol - pharmacology
Estrogens - pharmacology
Female
Gonadotropin-Releasing Hormone - analogs & derivatives
Gonadotropin-Releasing Hormone - pharmacology
Hormone Antagonists - pharmacology
Humans
Microvessels - drug effects
Microvessels - metabolism
Microvessels - physiology
Oligopeptides - pharmacology
Piperidines - pharmacology
Receptor, Endothelin B - metabolism
Skin - blood supply
Vasodilation
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Summary:The endothelin-B (ET ) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ET receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E ) on ET receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E exposure modulates ET receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m ) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E (0.1 mg/day, Vivelle-Dot patch) was added back on . We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on (GnRHant) and (GnRHant + E ) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ET receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ET receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ± 5%CVC , = 0.004). E administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant + E : 89 ± 8%CVC , = 0.036). Furthermore, cutaneous vasodilatory responses during ET receptor blockade were blunted after E administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVC , = 0.047). These data demonstrate that ovarian hormones, specifically E , modulate ET receptor function and contribute to the regulation of microvascular endothelial function in young women. The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00087.2021