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Abstract-Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to pregnancy are compromised. Oxidative stress as well as endothelial cell dysfunction have been implicated as pathophysiological features of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO). However, NO is also known to react with superoxide anions (produced under conditions of oxidative stress), yielding peroxynitrite that may impair vascular function. Our objective was to use immunohistochemical techniques to determine whether there is evidence of peroxynitrite formation in the maternal systemic vasculature of women with preeclampsia. Vessels were obtained from a biopsy of subcutaneous fat at the time of cesarean section from normal pregnant (nϭ7) and preeclamptic (nϭ7) women or at the time of hysterectomy from nonpregnant women (nϭ5). There were significantly more vessels staining with greater intensity for nitrotyrosine and endothelial NO synthase in the endothelium of vessels from women with preeclampsia compared with that of normal pregnant women or nonpregnant women. Both endothelial and smooth muscle cells from all vessels showed evidence for the presence of superoxide dismutase (SOD), an enzyme that scavenges superoxide anions. However, the intensity of staining for SOD in the endothelium was significantly lower in the preeclamptic and nonpregnant women than in normal pregnant women. These data of increased endothelial NO synthase, decreased SOD, and increased nitrotyrosine immunostaining in the maternal vasculature of women with preeclampsia suggest increased peroxynitrite formation. We speculate that peroxynitrite is involved in endothelial cell dysfunction in preeclamptic women and contributes to the pathophysiology of this pregnancy disorder. (Hypertension. 1999;33:83-89.)Key Words: endothelium Ⅲ nitric oxide synthase Ⅲ superoxide dismutase Ⅲ nitrotyrosine P reeclampsia is a common (Ϸ7% of all pregnancies) disorder of human pregnancy in which the normal hemodynamic response to pregnancy is compromised. It remains a leading cause of maternal morbidity and mortality and is associated with a significant increase in perinatal mortality. 1 It is diagnosed primarily by the onset of hypertension and proteinuria in the latter half of gestation. Other manifestations of preeclampsia include generalized vasoconstriction, increased vasoactivity, reduced perfusion to organs, and platelet activation.1 Both the etiology and pathophysiology of preeclampsia are poorly understood.There is accumulating evidence that a major component of the pathophysiology of preeclampsia is endothelial cell dysfunction.2 Endothelial cells produce a number of vasoactive substances to modulate vascular function, including the potent vasorelaxant nitric oxide (NO). Although pregnancy is a state of vasodilatation mediated in part by NO, 3 the role of NO in preeclampsia is not clear. Evidence for NO production in women with preeclampsia has been in conflict with reports of reduced, 4 unchanged, 5 or elevated 6...

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