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Am J Physiol Heart Circ Physiol 280: H1699-H1705, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 4, H1699-H1705, April 2001

Endothelial vasodilator production by uterine and systemic arteries. VII. Estrogen and progesterone effects on eNOS

Heidi L. Rupnow1, Terrance M. Phernetton1, Cynthia E. Shaw1, Mary L. Modrick1, Ian M. Bird1, and Ronald R. Magness1,2

Departments of 1 Obstetrics and Gynecology, Perinatal Research Laboratories, and 2 Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53715

Uterine blood flow (UBF) and uterine artery endothelial nitric oxide synthase (eNOS) expression are greatest during the follicular vs. luteal phase. 17beta -Estradiol (E2beta ) increases UBF and elevates eNOS in ovine uterine but not systemic arteries; progesterone (P4) effects on E2beta changes of eNOS remain unclear. Nonpregnant ovariectomized sheep received either vehicle (n = 10), P4 (0.9 g Controlled Internal Drug Release vaginal implants; n = 13), E2beta (5 µg/kg bolus + 6 µg · kg-1 · day-1; n = 10), or P4 + E2beta (n = 12). Reproductive (uterine/mammary) and nonreproductive (omental/renal) artery endothelial proteins were procured on day 10, and eNOS was measured by Western analysis. P4 and E2beta alone and in combination increased (P < 0.05) eNOS expression in uterine artery endothelium (vehicle = 100 ± 16%, P4 = 251 ± 59%, E2beta  = 566 ± 147%, P4 + E2beta  = 772 ± 211% of vehicle). Neither omental, renal, nor mammary artery eNOS was altered, demonstrating the local nature of steroid-induced maintenance of uterine arterial eNOS. In the myometrial microvasculature, eNOS was increased slightly (P = 0.06) with E2beta and significantly with P4 + E2beta . Systemic NOx was increased with P4 and P4 + E2beta , but not E2beta , suggesting differential regulation of eNOS expression and activity, since P4 increased eNOS in uterine artery endothelium while E2beta and the combination further increased eNOS protein.

nitric oxide; uterine blood flow; ovarian steroids; mammary; renal; omental; endothelial nitric oxide synthase


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