Regulation of types I and III NOS in ovine uterine arteries by daily and acute estrogen exposure

Abstract

Nitric oxide contributes to estrogen-mediated uterine vasodilation; however, the nitric oxide synthases (NOS) involved and their location within uterine arteries are incompletely documented. We investigated the effects of repetitive daily and acute estradiol-17β (E2β) exposure on uterine hemodynamics and NOS abundance and localization in uterine arteries from nonpregnant ovariectomized ewes receiving daily intravenous E2β (1 μg/kg, n = 5) or no E2β ( n = 7) for 5 days to determine NOS abundance, cGMP contents, and NOS immunohistochemistry. Daily E2β increased basal and E2β-mediated rises in uterine blood flow (UBF) 36 and 43% (<0.01), respectively, calcium-dependent NOS activity 150% ( P < 0.02) in endothelium-intact and -denuded (∼40% of total NOS) arteries, and cGMP contents 39% ( P < 0.05). Endothelial (eNOS) was detected in luminal endothelium, whereas neuronal NOS (nNOS) protein was only in the media. A second group of ewes received E2β (1 μg/kg iv) for 4 days and acute intravenous E2β ( n = 8) or vehicle ( n= 4) on day 5. UBF rose 5.5-fold ( P < 0.001) 115 min after E2β, at which time only endothelium-derived calcium-dependent NOS activity increased 30 ± 13% ( P < 0.05). Daily E2β enhances basal and E2β-mediated increases in UBF, which parallel increases in endothelium-derived eNOS and smooth muscle-derived nNOS. Acute E2β, however, selectively increases endothelium-derived eNOS.