Effects of 17-hydroxyprogesterone on tumor necrosis factor-α-induced hypertension during pregnancy

Abstract

BackgroundInflammatory cytokines such as tumor necrosis factor-α (TNF-α) may be an important link between placental ischemia and hypertension in preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP) on TNF-α-stimulated endothelin (ET) production and hypertension during pregnancy.MethodsTNF-α-stimulated ET was examined from endothelial cells cultured in the presence and absence of progesterone. Blood pressure and tissue ET-1 were measured in the following groups of pregnant rats: controls, 17-OHP (3.32 mg/kg), TNF-α treated (50 ng/day), TNF-α treated17-OHP.ResultsProgesterone abolished TNF-α-stimulated ET-1 from endothelial cells. TNF-α-induced hypertension was associated with significant increases in renal and placental ET-1. Administration of 17-OHP attenuated TNF-α-induced hypertension and decreased renal ET-1.ConclusionProgesterone directly abolished TNF-α-stimulated ET-1 and attenuated TNF-α-induced hypertension, possibly via suppression of the renal ET-1 system. These data suggest that treatment with progesterone of hypertension associated with elevated cytokines during pregnancy may be worthy of further consideration. © 2009 American Journal of Hypertension, Ltd.