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Am J Physiol Heart Circ Physiol 278: H2134-H2142, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 6, H2134-H2142, June 2000

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

Walid A. Salhab, Philip W. Shaul, Blair E. Cox, and Charles R. Rosenfeld

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75235

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 (E2beta ) exposure on uterine hemodynamics and NOS abundance and localization in uterine arteries from nonpregnant ovariectomized ewes receiving daily intravenous E2beta (1 µg/kg, n = 5) or no E2beta (n = 7) for 5 days to determine NOS abundance, cGMP contents, and NOS immunohistochemistry. Daily E2beta increased basal and E2beta -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 E2beta (1 µg/kg iv) for 4 days and acute intravenous E2beta (n = 8) or vehicle (n = 4) on day 5. UBF rose 5.5-fold (P < 0.001) 115 min after E2beta , at which time only endothelium-derived calcium-dependent NOS activity increased 30 ± 13% (P < 0.05). Daily E2beta enhances basal and E2beta -mediated increases in UBF, which parallel increases in endothelium-derived eNOS and smooth muscle-derived nNOS. Acute E2beta , however, selectively increases endothelium-derived eNOS.

endothelium; vascular smooth muscle; guanylyl cyclase; guanosine 3',5'-cyclic monophosphate


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