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Am J Physiol Heart Circ Physiol 275: H1845-H1856, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 5, H1845-H1856, November 1998

Endothelial vasodilator production by uterine and systemic arteries. III. Ovarian and estrogen effects on NO synthase

Karen E. Vagnoni1, Cynthia E. Shaw1, Terrance M. Phernetton1, Beth M. Meglin1, Ian M. Bird1, and Ronald R. Magness1,2

1 Perinatal Research Laboratories, Department of Obstetrics and Gynecology, and 2 Department of Meat and Animal Science, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53715

During the follicular phase of the ovarian cycle, when the local estrogen-to-progesterone ratio is elevated, uterine blood flow is elevated. This vasodilatory response is reproduced by exogenous 17beta -estradiol (E2beta ) administration via a nitric oxide (NO)-mediated mechanism. We hypothesized that endogenous ovarian estrogen and exogenous E2beta treatment elevate expression of endothelial cell-derived NO synthase (eNOS) in uterine, but not in systemic, arteries. Uterine, mammary, and systemic (renal and/or omental) arteries were collected from 1) ewes synchronized to the follicular (day -1 to day 0) or luteal (day 10) phases of the ovarian cycle (n = 4 per phase), 2) ovariectomized ewes 120 min after systemic vehicle or E2beta (5 µg/kg iv) treatment, and 3) ovariectomized ewes on days 0, 3, 6, 8, and 10 of E2beta (5 µg/kg iv, followed by 6 µg/kg per day) treatment. Expression of eNOS was localized primarily to the endothelium rather than vascular smooth muscle (VSM) in all arteries examined by immunohistochemistry and Western analysis; inducible NOS was not detected in either endothelium or VSM. Expression of eNOS protein was greater (P < 0.05) in uterine, but not in systemic, artery endothelium-isolated protein collected from follicular versus luteal phase ewes. Acute systemic E2beta treatment of ovariectomized ewes increased (P < 0.05) eNOS protein levels in uterine artery endothelium. Prolonged E2beta administration progressively increased uterine, but not systemic, artery endothelial eNOS protein expression. Therefore, the increased local estrogen-to-progesterone ratio during the follicular phase locally elevates eNOS expression, which possibly elevates uterine blood flow. These responses can be partly reproduced with E2beta administration.

ovary; uterine blood flow; steroids; nitric oxide; mammary; renal


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