Modulation of vascular tone by nitric oxide and endothelin 1 in myometrial resistance arteries from pregnant women at term.

Abstract

We evaluated the role of endothelium-derived nitric oxide and endothelin 1 in the modulation of myogenic tone, norepinephrine-induced tone, and flow-mediated responses in resistance arteries from pregnant women at term. Arteries (approximately 200 microm at 50 mm Hg; n = 27) were dissected from myometrial biopsies obtained from women undergoing elective cesarean delivery at term and mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and norepinephrine were studied in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine and the endothelin-converting enzyme inhibitor phosphoramidon. Pressure-induced (80 mm Hg) myogenic tone was significantly enhanced after incubation with Nomega-nitro-L-arginine (33% +/- 8% vs 24% +/- 4%; P <.05), whereas phosphoramidon significantly reduced myogenic tone (24% +/- 5% vs 33% +/- 5%; P <.05). A combination of Nomega-nitro-L -arginine and phosphoramidon did not affect myogenic tone. Norepinephrine-induced tone was significantly enhanced after nitric oxide synthase inhibition (49% +/- 6% vs 41% +/- 5%; P <.05) but was not affected by phosphoramidon. Flow-mediated dilatation was increased in the presence of phosphoramidon compared with flow-induced dilatation in physiologic salt solution (maximum dilatation, 57% +/- 12% vs 30% +/- 5%; analysis of variance, P <.05), and all flow-induced dilatation was abolished by Nomega-nitro-L -arginine. Nitric oxide and endothelin 1 may play a significant role in modulation of myogenic tone and flow-mediated responses in the resistance vasculature of the uterine circulation in normal pregnancy.