ET Receptor Contribution to Vascular Dysfunction in Postmenopausal Women

Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via the ET receptor. However, there are sex differences in the ET-1 system, and ET receptors are modulated by sex hormones. The purpose of this study was to test the hypothesis that ET receptors contribute to impaired vasodilatory function in postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating (42°C) via laser Doppler flowmetry in 18 young women (YW; 22 ± 1 yr) and 16 PMW (56 ± 1 yr). Cutaneous microdialysis perfusions of lactated Ringer (control), an ET receptor antagonist (BQ-788, 300 nM), and an ET receptor antagonist (BQ-123, 500 nM), were done through separate fibers, followed by perfusions of sodium nitroprusside (28 mM) and local heating to 43°C (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial pressure and expressed as a percent of maximal dilation. FMD (YW: 7.5 ± 0.5 vs. PMW: 5.6 ± 0.6%) and cutaneous vasodilation (YW: 93 ± 2 vs. PMW: 83 ± 4%CVC) were lower in PMW (both < 0.05). Blockade of ET receptors decreased cutaneous vasodilation in YW (87 ± 2%CVC; < 0.05 vs. control) but increased vasodilation in PMW (93 ± 1%CVC; < 0.05 vs. control). ET receptor blockade had minimal effect in YW (92 ± 1%CVC) but increased cutaneous vasodilation in PMW (91 ± 2%CVC; < 0.05 vs. control). In conclusion, ET receptors mediate vasodilation in YW, but this effect is lost after menopause. Impaired vasodilatory function in PMW is due in part to a loss of ET-mediated dilation.