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

Walid A. Salhab, W A Salhab, Philip W. Shaul, P W Shaul, B E Cox, Blair E. Cox, Charles R. Rosenfeld, C R Rosenfeld
American journal of physiology. Heart and circulatory physiology · 2000 · vol. 278(6) , pp. H2134–H2142 · doi:10.1152/ajpheart.2000.278.6.h2134 · PMID:10843913 · W2208568497
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Daily and acute estradiol exposure in ovariectomized ewes increased uterine blood flow by enhancing endothelial nitric oxide synthase activity, while daily treatment additionally elevated neuronal nitric oxide synthase in the vascular media.

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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-17beta (E(2)beta) exposure on uterine hemodynamics and NOS abundance and localization in uterine arteries from nonpregnant ovariectomized ewes receiving daily intravenous E(2)beta (1 microg/kg, n = 5) or no E(2)beta (n = 7) for 5 days to determine NOS abundance, cGMP contents, and NOS immunohistochemistry. Daily E(2)beta increased basal and E(2)beta-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 ( approximately 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 E(2)beta (1 microg/kg iv) for 4 days and acute intravenous E(2)beta (n = 8) or vehicle (n = 4) on day 5. UBF rose 5.5-fold (P < 0.001) 115 min after E(2)beta, at which time only endothelium-derived calcium-dependent NOS activity increased 30 +/- 13% (P < 0.05). Daily E(2)beta enhances basal and E(2)beta-mediated increases in UBF, which parallel increases in endothelium-derived eNOS and smooth muscle-derived nNOS. Acute E(2)beta, however, selectively increases endothelium-derived eNOS.

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MeSH descriptors

Estradiol Nitric Oxide Synthase Uterus Animals Arteries Arteries Arteries Cyclic GMP Cyclic GMP Drug Administration Schedule Estradiol Estradiol Female Injections, Intravenous Nitric Oxide Synthase Nitric Oxide Synthase Type I Nitric Oxide Synthase Type III Regional Blood Flow Regional Blood Flow Sheep

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