Endothelium-derived nitric oxide is proposed to play an important role in the lowering of peripheral vascular resistance in normal pregnancy. In women with preeclampsia, the function of the endothelium is compromised, and it is suggested that reduced nitric oxide synthesis may contribute to the elevation of blood pressure and activation of coagulation pathways. In this study, we have compared responses to increments of intraluminal flow, considered to be a physiological stimulus to nitric oxide release, in arteries from normotensive nonpregnant and pregnant women and women with preeclampsia. Small subcutaneous arteries from normotensive pregnant women showed substantial flow-induced relaxation, which was attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (mean relaxation, 48.3+/-8.0% [absence of L-NAME] versus 19.2+/-10.6% [presence of L-NAME]), whereas those from nonpregnant women and women with preeclampsia demonstrated modest constriction (mean constriction, 10.1+/-7.3% and 1.2+/-7.2%, respectively). Shear stress, the frictional force that is the stimulus for flow responses, was calculated from parameters of flow, viscosity, and artery diameter. Arteries from pregnant women showed greater relaxation to shear than those from nonpregnant women or those with preeclampsia. We conclude that flow-induced shear stress is a potent stimulus to vasodilatation in arteries from pregnant women and that this mechanism may lead to a fall in peripheral vascular resistance in normal pregnancy. Failure of this flow-induced dilatation may contribute to the gestational hypertension of preeclampsia.

Objective To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction.Design Syncytiotrophoblast microvillous membrane (STBM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholineinduced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion.Sample STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term.Results Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption.Conclusions STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfimction observed in the maternal syndrome of pre-eclampsia.

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1. The mechanisms of vascular adaptation to pregnancy remain to be fully elucidated. In this study we L-NAME, n = 8; n.s.). This was also reflected in a greater response to shear stress in the arteries from pregnant animals. 5. We conclude that myogenic tone is not significantly different in pregnant and non-pregnant resistance sized mesenteric arteries of Wistar rats. However, flow-induced dilatation, mediated by nitric oxide release, may play a major role in lowering vascular resistance during pregnancy.In normal human pregnancy the cardiac output rises by 40% and the blood volume by 45-55%, but despite this, the blood pressure falls reaching its nadir in the second trimester (Halligan et al. 1993). The lowering of blood pressure is achieved by a substantial reduction in the peripheral vascular resistance, but the pathways underlying this physiological adaptation to the state of pregnancy remain unknown. A number of contributory mechanisms have been proposed, including a reduction of myogenic tone (Meyer, Brayden & McLaughlin, 1993) and an increase in vasodilatation through enhanced release of nitric oxide (NO). A role for NO has been implied by the increased response to endothelium-dependent vasodilator agonists, including acetylcholine (ACh) in the carotid and uterine arteries of the pregnant guinea-pig (Weiner, Martinez, Liu,