Mechanism of Vascular Dysfunction Due to Circulating Factors in Women With Preeclampsia [23O]

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Circulating factors have been proposed to play a major role in the pathophysiology of endothelial dysfunction observed in preeclampsia (PE), defined as new-onset hypertension with proteinuria after 20 weeks of gestation. We hypothesized that circulating factors in PE plasma lead to endothelial dysfunction by increasing oxidative stress and reducing nitric oxide and prostaglandin bioavailability.


Pregnant rat uterine and mesenteric arteries were incubated overnight with 3% normotensive (NP) or PE plasma collected from pregnant women. Responses to methacholine were obtained using wire myography to assess endothelial function pathways. Vascular superoxide production was measured via dihydroethidium staining and nitric oxide synthase (NOS) expression via Western blots.


PE plasma significantly increased superoxide production and impaired endothelial function in uterine arteries (Emax 79.9±5.6% vs 44.9±6.3%, P=.0004), which was restored in the presence of oxidant scavengers or prostaglandin synthesis inhibition. Uterine artery vasodilation was abolished in the presence of pan nitric oxide synthase inhibition in both NP- and PE-treated vessels, but inducible NOS (iNOS)-dependent vasodilation was present only in NP-treated arteries. Uterine arteries exposed to PE plasma exhibit an increased endothelial NOS expression and a decreased iNOS expression. PE plasma did not alter endothelial function in mesenteric arteries, suggesting the effect of circulating factors on endothelial function was vascular bed specific.


We have shown that circulating factors contribute to endothelial dysfunction via altered oxidative stress and vasodilator pathways. This study contributes to understanding the pathophysiology and finding a potential target for intervention in PE.

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