Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women, , ,

Objective: Our purpose was to evaluate flow-induced responses, myogenic tone, and norepinephrine-induced constriction in myometrial resistance arteries from normal term pregnant women and the role that nitric oxide and prostanoids may play in these responses. Study Design: Arteries (approximately 200 μm, n = 14, at 40 mm Hg) were dissected from myometrial biopsy specimens from women undergoing cesarean section and then were mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine 10−6 mol/L) were studied in the absence and presence of Nω-nitro-l-arginine methyl ester (n = 7) or indomethacin (n = 5). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium. Results: Arteries developed myogenic tone (80 mm Hg) that was not modulated by nitric oxide or prostanoid release, whereas norepinephrine-induced tone was significantly enhanced by the nitric oxide inhibitor. An increase in intraluminal flow led to dilatation in physiologic salt solution and indomethacin, but to constriction in the presence of Nω-nitro-l-arginine methyl ester (percent increase in diameter at flow rate of 184.6 μl/min, 24% ± 8% in physiologic salt solution and 20% ± 4% in the presence of indomethacin versus –27% ± 12% in Nω-nitro-l-arginine methyl ester alone and –21% ± 10% in indomethacin and Nω-nitro-l-arginine methyl ester, respectively, analysis of variance, p< 0.05). Conclusions: Flow-induced shear stress is a physiologic modulator of vascular tone in myometrial arteries from pregnant women. Nitric oxide, but not prostanoids, mediates this response and also blunts norepinephrine constriction. Nitric oxide may play a fundamental role in the maintenance of adequate blood supply to the fetus during human pregnancy.