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 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 micrograms/kg iv) treatment, and 3) ovariectomized ewes on days 0, 3, 6, 8, and 10 of E2beta (5 micrograms/kg iv, followed by 6 micrograms/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.
Vagnoni
K E
KE
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53715, USA.
Shaw
C E
CE
Phernetton
T M
TM
Meglin
B M
BM
Bird
I M
IM
Magness
R R
RR
D000818:Animals; D001158:Arteries / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D012756:Sheep; D014599:Uterus / Q000502:physiology*
D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III