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Endothelin‐1 Receptor Responses during the Menstrual Cycle
Author(s) -
Sebzda Kelly N,
Wenner Megan M
Publication year - 2016
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.30.1_supplement.736.9
Subject(s) - luteal phase , endothelin receptor , endocrinology , medicine , microdialysis , endothelin 1 , vasodilation , receptor , menstrual cycle , chemistry , hormone , central nervous system
Endothelin‐1 (ET‐1) is involved in regulating vascular function through two receptor subtypes: endothelin A (ET‐A) and endothelin B (ET‐B). Studies in animal and cell models suggest that ovarian hormones, such as estradiol (E 2 ) and progesterone (P 4 ), modulate differences in ET‐1 mediated vasomotor function. However, these mechanisms have not been comprehensively examined in humans. Therefore, the purpose of this study was to test the hypothesis that ovarian hormones would mediate microvascular vasodilation through an ET‐B receptor mechanism. We measured microvascular vasodilatory responses (% CVCmax) during local skin warming via laser Doppler flowmetry coupled with intradermal microdialysis perfusions of lactated Ringers (control), ET‐B (BQ‐788, 300nM), and ET‐A (BQ‐123, 500nM) receptor antagonists in ten young women (21±1 years, 23±1 kg/m 2 , 85±2 mmHg resting mean blood pressure) during the mid‐luteal (ML; days 20–25) and early follicular (EF; days 2–6) phases of the menstrual cycle. As expected, serum E 2 (ML: 132.9±19.7 vs. EF: 51.1±10.6 pg/ml, P < 0.05) and P 4 (ML: 6.8±1.5 vs. EF: 0.9±0.2 ng/ml, P < 0.05) levels were higher in women during the ML compared to the EF visit. ET‐B receptor blockade decreased vasodilatory responses during the ML phase (control: 91.0±1.9 vs. BQ‐788: 84.4±2.1% CVCmax, P < 0.05) but not during the EF phase (control: 88.5±2.4 vs. BQ‐788: 88.9±1.2% CVCmax, P = 0.88). ET‐A receptor blockade tended to decreased vasodilatory responses during the ML phase (control: 91.0±1.9 vs. BQ‐123: 87.7±1.8% CVCmax, P = 0.09) but not during the EF phase (control: 88.5±2.4 vs. BQ‐123: 92.2±2.4% CVCmax, P = 0.20). These data suggest that ET‐B receptors mediate vasodilation during the ML phase of the menstrual cycle, when both E 2 and P 4 are elevated. Additional studies are needed to determine the direct influence of E 2 and P 4 on ET‐B receptor function. Support or Funding Information Supported by NIH Grant U54 GM 104941 01A1 and University of Delaware Research Foundation