Ovarian hormones modulate endothelin-1 receptor responses in young women

Objective: We recently demonstrated ETBR mediate vasodilation in young but not postmenopausal women; it is unclear if this is related to age or a decline in ovarian hormones. The purpose of this study was to test the hypothesis that ETBR responses are modulated by ovarian hormones. Methods: We measured cutaneous vasodilatory responses in 12 young women (22 +/- 1 years, 23 +/- 1 kg/m(2)) during the ML (days 20-25) and EF (days 2-5) phases of the menstrual cycle. Cutaneous microdialysis perfusions of lactated Ringer (control), ETBR antagonist (BQ-788, 300 nmol/L), and ETA(R) antagonist (BQ-123, 500 nmol/L) were performed, followed by local heating to 42 degrees C. Results: Serum estradiol (ML: 118 +/- 16 vs EF: 44 +/- 9 pg/mL, P < 0.05) and progesterone (ML: 8.3 +/- 1.0 vs EF: 0.7 +/- 0.2 ng/mL, P < 0.05) were higher during ML vs EF phase. ETBR blockade decreased vasodilation during ML (control: 91 +/- 2 vs BQ-788: 83 +/- 2% CVCmax, P < 0.05) but not EF (control: 89 +/- 2 vs BQ-788: 89 +/- 1%CVCmax). ETA(R) blockade also decreased vasodilation during ML (control: 91 +/- 2 vs BQ-123: 87 +/- 2% CVCmax, P < 0.05) but not EF (control: 89 +/- 2 vs BQ-123: 92 +/- 2% CVCmax). Conclusions: These data suggest that fluctuations in ovarian hormones modulate ETBR and ETA(R) responses in young women.