ENDOTHELIAL VASODILATOR PRODUCTION BY UTERINE AND SYSTEMIC ARTERIES -III - OVARIAN AND ESTROGEN EFFECTS ON NO SYNTHASE

During the follicular phase of the ovarian cycle, when the local estro gen-to-progesterone ratio is elevated, uterine blood flow is elevated. This vasodilatory response is reproduced by exogenous 17 beta-estradi ol (E(2)beta) administration via a nitric oxide (NO)-mediated mechanis m. We hypothesized that endogenous ovarian estrogen and exogenous E(2) beta treatment elevate expression of endothelial cell-derived NO synth ase (eNOS) in uterine, but not in systemic, arteries. Uterine, mammary , and systemic (renal and/or omental) arteries were collected from I) ewes synchronized to the follicular (day -1 to day 0) or luteal (day 1 0) phases of the ovarian cycle (n = 4 per phase), 2) ovariectomized ew es 120 min after systemic vehicle or E(2)beta (5 mu g/kg iv) treatment , and 3) ovariectomized ewes on days 0, 3, 6, 8, and 10 of E(2)beta (5 mu g/kg iv, followed by 6 mu g/kg per day) treatment. Expression of e NOS was localized primarily to the endothelium rather than vascular sm ooth muscle (VSM) in all arteries examined by immunohistochemistry and Western analysis; inducible NOS was hot detected in either endotheliu m or VSM. Expression of eNOS protein was greater (P < 0.05) in uterine , but not in systemic, artery endothelium-isolated protein collected f rom follicular versus luteal phase ewes. Acute systemic E(2)beta treat ment of ovariectomized ewes increased (P < 0.05) eNOS protein levels i n uterine artery endothelium. Prolonged E(2)beta administration progre ssively increased uterine, but not systemic, artery endothelial eNOS p rotein expression. Therefore, the increased local estrogen-to-progeste rone ratio during the follicular phase locally elevates eNOS expressio n, which possibly elevates uterine blood flow. These responses can be partly reproduced with E(2)beta administration.