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

Objective: The mechanism(s) by which magnesium sulfate (MgSO4) functio ns clinically to prevent eclamptic seizures in severe pregnancy-induce d hypertension (PIH) is unknown; however, it has been reported to both enhance and inhibit prostacyclin (PGI(2)) production by umbilical vei n endothelial cells. Because PGI(2) is decreased in patients with PIH, we tested the hypothesis that MgSO4 increases vasodilatory prostaglan dins [PGI(2) and prostaglandin (PGF(2)] relative to vasconstrictor eic osanoids [thromboxane (Tx)A(2) and PGF(2 alpha)] in patients with PIH. Methods: In 11 women with PM (28-40 weeks' gestation), MgSO4 was admi nistered i.v. as a 4-g loading dose, followed by 2 g/h continuous infu sion. Plasma samples were obtained before and at 2 and 4 h of MgSO4 tr eatment. 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 plasm a 6-keto-PGF(1 alpha) levels and 6-keto-PGF(1 alpha)/TxB(2) ratios ave raged 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+/-1 7 pg/mL and 0.47+/-0.13, respectively, and then rebounded by 4 h to 31 6+/-122 pg/mL and 1.93+/-0.74, respectively. Although plasma TxB(2) an d PGE(2) levels were unchanged by MgSO4 therapy (P>0.05), this treatme nt 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 result ed in a modest but statically significant reduction in circulating lev els of PGF(2 alpha).