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ET‐1 Receptor Function in Women with Advancing Reproductive Age
Author(s) -
McGinty Shane J.,
Welti Laura M.,
Kuczmarski Andrew V.,
Shoemaker Lee.,
Moreau Kerrie L.,
Wenner Megan M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05481
Subject(s) - vasodilation , medicine , sodium nitroprusside , endothelin 1 , endothelial dysfunction , endocrinology , perfusion , blockade , receptor , endothelin receptor , microdialysis , cardiology , nitric oxide , central nervous system
Endothelin‐1 (ET‐1) contributes to endothelial dysfunction, a primary driver of hypertension and cardiovascular disease. Our lab has previously shown that the ET B receptor mediates vasodilation in premenopausal women (PRE), but this effect is lost in postmenopausal women (POST). Noticeable declines in endothelial function are evident early in the menopausal transition, but the function of the ET B receptor in perimenopausal women (PERI) is unclear. PURPOSE The purpose of this study was to test the hypothesis that ET B ‐mediated vasodilation progressively declines with advancing reproductive age in women. METHODS We used the STRAW+10 staging criteria to classify women as PRE (n=12, 26±2 yrs, 23±1 kg/m 2 , 83±2 mmHg), PERI (n=9, 50±1 yrs, 24±1 kg/m 2 , 84±3 mmHg), or POST (n=11, 56±1 yrs, 24±1 kg/m 2 , 87±2 mmHg). Cutaneous vasodilatory responses to local heating were measured using laser doppler flowmetry during microdialysis perfusions of lactated Ringer’s (Control), ET B receptor blockade (BQ‐788, 300nM), and ET A receptor blockade (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. RESULTS PRE showed the greatest cutaneous vasodilation in response to local heating (PRE: 93±2; PERI: 84±2; POST: 88±2 %CVC max, P <0.05 vs PERI and POST). There was a trend for increased vasodilatory responses to ET B receptor blockade with advancing reproductive age (PRE: 85±3; PERI: 91±2; POST: 92±3 %CVC max, P =0.13). However, there were no differences in vasodilatory responses during ET A receptor blockade (PRE: 90±2; PERI: 91±3; POST: 92±3 %CVC max, P =0.84). Finally, brachial artery flow‐mediated dilation tended to decline (PRE: 7±1; PERI: 6±1; POST: 5±1 %Δ, P =0.09) while pulse wave velocity increased with advancing reproductive age (PRE: 6±0; PERI: 7±0; POST: 7±0 m/s, P <0.05 vs PERI and POST). CONCLUSIONS These preliminary data suggest that adverse changes in vascular function, and potentially ET B receptor function, are evident early in PERI. Therefore, future research examining the role of the ET‐1 pathway in progressive vascular dysfunction throughout the menopausal transition is warranted. Support or Funding Information NIH R01 HL 146558, P20 GM 113125