REGULATION OF ENDOMETRIAL BLOOD-FLOW IN OVARIECTOMIZED RATS - ASSESSMENT OF THE ROLE OF NITRIC-OXIDE

The purpose of this study was to evaluate the role of nitric oxide (NO ) in the maintenance of basal endometrial blood flow of ovariectomized rats and in the increase of endometrial blood flow after administrati on of estradiol 17 beta (E-2 beta). Endometrial blood flow was repeate dly measured with the H-2 gas clearance technique in ovariectomized ra ts. N-omega-nitro-L-arginine methyl ester (L-NAME) dose dependently re duced basal endometrial blood flow and increased mean arterial blood p ressure and endometrial vascular resistance. E-2 beta (1 mu g/kg iv) i ncreased endometrial blood flow and reduced endometrial vascular resis tance, which peaked by 2 h after the injection. The vasoconstrictive a ctivity of L-NAME (an inhibitor for NO synthesis) was compared with th at of phenylephrine (PE, an a-receptor agonist acting through an NO-in dependent mechanism). Doses of L-NAME (1 and 3 mg/kg iv) were matched with those of PE (3.2 and 6.4 mg.kg(-1).h(-1) iv), as they induced an approximately equivalent percent increase in basal endometrial vascula r resistance. The percent increases of endometrial vascular resistance in E-2 beta-treated animals by the two agents in matched doses were a lso of a similar magnitude. When animals were first treated with L-NAM E or PE, E-2 beta lost the ability to reduce endometrial vascular resi stance. Enzyme activity and gene expression of NO synthase in the rat uterine tissue were also examined after E-2 beta treatment, and no sig nificant changes were observed. These data raise doubts about the role of NO in the regulation of endometrial blood flow after acute adminis tration of E-2 beta and suggest that other mechanisms may be involved.