Ovarian hormones modulate endothelin-1 receptor responses in young women.

ABSTRACT

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/m2 ) 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 ETAR antagonist (BQ-123, 500 nmol/L) were performed, followed by local heating to 42°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). ETAR 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 ETAR responses in young women.