Abstract
Preeclampsia is a disorder of pregnancy characterized clinically by hypertension, proteinuria, and edema and characterized pathologically in its late stages by widespread microvascular thrombi. There is evidence from a number of studies that production of prostacyclin (prostaglandin I2, PGI2), a potent vasodilator and inhibitor of platelet aggregation, is deficient in preeclamptic compared to normal pregnancy. Traditional therapy utilizes infusions of large amounts of MgSO4, but the physiologic basis for this is not clear. We studied the effect of MgSO4 on PGI2 release by cultured human umbilical vein endothelial cells (HUVEC) by several methods. By platelet aggregometry, the known antiaggregatory effect of intact HUVEC was enhanced by MgSO4. By radioimmunoassay for 6-keto-PGF1 alpha, the stable metabolite of PGI2, it was shown that MgSO4 amplifies release of PGI2 by HUVEC in a dose-dependent manner, with a peak occurring between 2 and 3 mM. In separate experiments, MgSO4 overcame the enhanced adherence of platelets to HUVEC exhausted by repeated exposure to thrombin. Finally, PGI2 production was 2- to 5-fold greater by HUVEC incubated with plasma obtained from preeclamptic patients undergoing MgSO4 therapy than by HUVEC incubated with pretherapy plasma. We conclude that MgSO4 mediates enhanced production of PGI2 by vascular endothelium, thereby potentially enhancing its thromboresistant properties.
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