EFFECT OF MAGNESIUM-SULFATE ON EICOSANOID LEVELS IN WOMEN WITH PREGNANCY-INDUCED HYPERTENSION

Objective: The mechanism(s) by which magnesium sulfate (MgSO4) functions clinically to prevent eclamptic seizures in severe pregnancy-induced hypertension (PIH) is unknown; however, it has been reported to both enhance and inhibit prostacyclin (PGI(2)) production by umbilical vein endothelial cells. Because PGI(2) is decreased in patients with PIH, we tested the hypothesis that MgSO4 increases vasodilatory prostaglandins [PGI(2) and prostaglandin (PGF(2)] relative to vasconstrictor eicosanoids [thromboxane (Tx)A(2) and PGF(2 alpha)] in patients with PIH. Methods: In 11 women with PM (28-40 weeks' gestation), MgSO4 was administered i.v. as a 4-g loading dose, followed by 2 g/h continuous infusion. Plasma samples were obtained before and at 2 and 4 h of MgSO4 treatment. Main Outcome Measures: We measured the effects of i.v. MgSO4 on plasma 6-keto-PGF(1 alpha), TxB(2) (metabolites of PGI(2) and TxA(2), respectively), PGE(2), and PGF(2 alpha). Results: The control plasma 6-keto-PGF(1 alpha) levels and 6-keto-PGF(1 alpha)/TxB(2) ratios averaged 220+/-38 pg/mL and 1.41+/-0.35, respectively ((x) over bar+/-SEM); they were decreased (P=0.03) after 2 h i.v. MgSO4 therapy to 77+/-17 pg/mL and 0.47+/-0.13, respectively, and then rebounded by 4 h to 316+/-122 pg/mL and 1.93+/-0.74, respectively. Although plasma TxB(2) and PGE(2) levels were unchanged by MgSO4 therapy (P>0.05), this treatment decreased CP=0.05) plasma PGF(2 alpha) concentrations from 131+/-25 pg/mL to 90+/-21 pg/mL at 2 h and to 87+/-16 pg/mL at 4 h. Conclusion: These in vivo data obtained from women with PIH are consistent with in vitro observations that MgSO4 may either inhibit or stimulate PGI(2) production by endothelial cells. Additionally, MgSO4 infusion resulted in a modest but statically significant reduction in circulating levels of PGF(2 alpha).