Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis.

Abstract

Our study was designed to determine whether nitric oxide mediates estrogen-induced increases in uterine blood flow. 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. 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. 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.