Effect of Magnesium Sulfate on Eicosanoid Levels in Women with Pregnancy-Induced Hypertension

Abstract

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 (PGI₂) production by umbilical vein endothelial cells. Because PGI₂ is decreased in patients with PIH, we tested the hypothesis that MgSO₄ increases vasodilatory prostaglandins [PGI₂ and prostaglandin (PG)E₂] relative to vasoconstrictor eicosanoids [thromboxane (Tx)A₂ and PGF₂aL] in patients with PIH.

Methods: In 11 women with PIH (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-PGF₁aL, TxB₂ (metabolites of PGI₂ and TxA₂, respectively), PGE₂, and PGF₂aL.

Results: The control plasma 6-keto-PGF₁aL levels and 6-keto-PGF₁aL/TxB₂ ratios averaged 22038 pg/mL and 1.410.35, respectively (SEM); they were decreased (P=0.03) after 2 h i.v. MgSO₄ therapy to 7717 pg/mL and 0.470.13, respectively, and then rebounded by 4 h to 316122 pg/mL and 1.930.74, respectively. Although plasma TxB₂ and PGE₂ levels were unchanged by MgSO₄ therapy (P>0.05), this treatment decreased (P=0.05) plasma PGF₂aL concentrations from 13125 pg/mL to 9021 pg/mL at 2 h and to 8716 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 PGI₂ production by endothelial cells. Additionally, MgSO₄ infusion resulted in a modest but statically significant reduction in circulating levels of PGF₂aL.

Key Words:

• Eicosanoids
• Hypertension
• Magnesium sulfate
• Preeclampsia
• Pregnancy