Session: 589 APS Cardiovascular and Exercise Endocrinology Poster Session
(589.3) Effect of Short-Term Estradiol Exposure on Endothelin-B Receptor-Mediated Vasodilation in Postmenopausal Women
Sunday, April 3, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E364
Laura Welti (University of Delaware), Katherine Haigh (University of Delaware), Shane McGinty (University of Delaware), Angelica Del Vecchio (University of Delaware), David Edwards (University of Delaware), Megan Wenner (University of Delaware)
Endothelin (ET)-1 contributes to endothelial dysfunction in postmenopausal women (PMW) via the ETB receptor. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost in PMW. However, it is unclear if ETB receptor-mediated dilation can be restored in PMW exposed to E2.
Purpose: To test the hypothesis that E2 exposure restores ETB receptor-mediated vasodilation in PMW.
Methods: We tested 9 PMW (55±2 yrs, 24±3 kg/m2, 91±5 mmHg) who self-reported natural menopause and were at least 1 year without menses. We measured vasodilation in the cutaneous microcirculation via local heating using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer’s (control), ETB receptor antagonist (BQ-788, 300nM) and ETA receptor antagonist (BQ-123, 500nM). Cutaneous vascular conductance (CVC) was calculated during the plateau phase of local heating (42°C), and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. All women were tested at baseline (BL) and after 7 days of E2 (Vivelle-Dot, 0.1mg/day, transdermal patch) administration (+E2). A two-way repeated measures ANOVA was performed to compare %CVCmax in PMW before and after E2 exposure. Data presented are mean ± standard deviation.
Results: E2 administration increased serum estradiol (BL: 45±29 vs +E2: 71±42 pg/mL, Plt;0.01) and reduced follicle stimulating hormone (BL: 71±13 vs +E2: 57±17 pg/mL, Plt;0.01), but there were no changes in serum progesterone (BL: 0.57±0.93 vs +E2: 0.53±0.88 pg/mL, P=0.14) nor plasma ET-1 (BL: 1.62±0.66 vs +E2: 1.54±0.54 pg/mL, P=0.42). E2 administration had no effect on cutaneous microvascular responses (Time P=0.41, Drug P=0.17, Interaction P=0.71). At BL, vasodilatory responses to local heating were not different during control and ETB receptor antagonism (control: 83±8 vs. BQ-788: 88±6 %CVCmax). Similarly, vasodilation was not altered at BL during ETA receptor antagonism in a subset of women (n=6, control: 83±8 vs. BQ-123: 87±8 %CVCmax). E2 administration did not improve vasodilation in the control site (BL: 83±8 vs. +E2 85±13 %CVCmax). Furthermore, there was no effect of E2 exposure on cutaneous vasodilatory responses during perfusion of ETB (BL: 88±6 vs. +E2: 89±6 %CVCmax) nor ETA (n=6, BL: 87±8 vs +E2: 92±7 %CVCmax) receptor antagonists.
Conclusion: These preliminary data suggest that short-term E2 exposure does not modulate ETB receptor function in PMW. These findings are in contrast to our observations in young women demonstrating that ETB receptors mediate vasodilation in the presence of E2. The role of alternative therapies to modulate ETB receptor function should be considered in future studies.
