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

Abstract

Uterine blood flow (UBF) and uterine artery endothelial nitric oxide synthase (eNOS) expression are greatest during the follicular vs. luteal phase. 17β-Estradiol (E2β) increases UBF and elevates eNOS in ovine uterine but not systemic arteries; progesterone (P4) effects on E2β 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), E2β (5 μg/kg bolus + 6 μg · kg−1 · day−1; n = 10), or P4 + E2β ( 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 E2β alone and in combination increased ( P < 0.05) eNOS expression in uterine artery endothelium (vehicle = 100 ± 16%, P4 = 251 ± 59%, E2β = 566 ± 147%, P4 + E2β = 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 E2β and significantly with P4 + E2β. Systemic NOx was increased with P4 and P4 + E2β, but not E2β, suggesting differential regulation of eNOS expression and activity, since P4 increased eNOS in uterine artery endothelium while E2β and the combination further increased eNOS protein.