Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis.
OBJECTIVE
Our study was designed to determine whether nitric oxide mediates estrogen-induced increases in uterine blood flow.


METHODS
Six nonpregnant oophorectomized ewes were instrumented with uterine artery flow probes and catheters. Ewes received estradiol-17 beta 1 microgram/kg, which maximally increased uterine blood flow by 120 minutes. Each animal then received local bolus injections of the nitric oxide synthetase inhibitor L-nitroarginine methyl ester.


RESULTS
Estradiol-17 beta increased uterine blood flow from 16 +/- 6 to 139 +/- 32 ml/min by 120 minutes. Local uterine artery administration of L-nitroarginine methyl ester (1 to 30 mg) caused a dose-related decrease in uterine blood flow, which reached a maximum of 59% +/- 6% inhibition. Higher doses of L-nitroarginine methyl ester less than or equal to 10 mg/kg (330 to 460 mg) given locally led to a maximum inhibition of 79% +/- 3% but showed systemic responses.


CONCLUSIONS
Estradiol-17 beta-induced increases in uterine blood flow are mediated mainly by nitric oxide; the observed vasodilation can be antagonized by the intraaterial administration of nitric oxide synthetase inhibitor L-nitroarginine methyl ester.
Van Buren
G A
GA
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526.
Yang
D S
DS
Clark
K E
KE
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep / Q000097:blood; D014599:Uterus / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D004958:Estradiol; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester