Preeclampsia: evidence for impaired shear stress-mediated nitric oxide release in uterine circulation.

OBJECTIVE: We sought to compare flow-mediated dilatation and myogenic and norepinephrine-induced tone in myometrial resistance arteries from women with preeclampsia and healthy pregnant women and to evaluate the role that nitric oxide may play in these responses. STUDY
DESIGN: Arteries (approximately 200 microm, at 50 mm Hg) were dissected from myometrial biopsy specimens from women undergoing emergency cesarean delivery because of preeclampsia (n = 6) and from healthy control subjects undergoing planned cesarean delivery (n = 9). Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine, 10(-6) mol/L) were studied in the absence and presence of the nitric oxide synthase inhibitor N omeganitro-L -arginine (10(-4) mol/L). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium and in the presence of papaverine (10(-4) mol/L).
RESULTS: An increase in intraluminal flow led to dilatation of isolated myometrial arteries from healthy gravid women, whereas flow-mediated dilatation was absent in arteries from gravid patients with preeclampsia (increase in diameter at maximum flow rate of 204 microL/min, 28% +/- 5% in healthy gravid patients vs -15% +/- 6% in gravid women with preeclampsia; analysis of variance, P <.05). Addition of N omega-nitro-L -arginine had no significant effect on flow-mediated responses in arteries from women with preeclampsia, whereas flow-mediated dilatation was abolished after addition of N omega-nitro-L -arginine in arteries from healthy gravid women (increase in diameter at a maximum flow rate of 204 microL/min, 28% +/- 5% control vs -9% +/- 5% N omega-nitro-L -arginine; analysis of variance, P <.05). Arteries from women with preeclampsia developed pressure-induced myogenic and norepinephrine-induced tone, similar to that obtained in arteries from healthy gravid women. In arteries from gravid women with preeclampsia, inhibition of nitric oxide synthase enhanced myogenic-induced tone (25% +/- 4% control vs 35% +/- 5% N omega-nitro-L -arginine; P <.05) and norepinephrine-induced tone (36% +/- 4% control vs 46% +/- 6% N omega-nitro-L -arginine; P <.05), as in arteries from healthy gravid women.
CONCLUSIONS: Nitric oxide may participate in modulation of pressure- and norepinephrine-induced tone even in preeclampsia, but the shear stress-mediated release of nitric oxide is absent. Failure of shear stress-mediated dilation in myometrial arteries from gravid women with preeclampsia might contribute to the impaired uteroplacental blood flow in this disease.