Magnesium sulfate: Rationale for its use in preeclampsia

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 vaodilator 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(α), 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.