Effects of 17-hydroxyprogesterone on tumor necrosis factor-alpha-induced hypertension during pregnancy
Sharon D Keiser1, Edward W Veillon, Marc R Parrish
1Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Background:
Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) may be an important link between placental ischemia and hypertension in preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP) on TNF-alpha-stimulated endothelin (ET) production and hypertension during pregnancy.
Methods:
TNF-alpha-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-alpha treated (50 ng/day), TNF-alpha treated+17-OHP.
Results:
Progesterone abolished TNF-alpha-stimulated ET-1 from endothelial cells. TNF-alpha-induced hypertension was associated with significant increases in renal and placental ET-1. Administration of 17-OHP attenuated TNF-alpha-induced hypertension and decreased renal ET-1.
Conclusion:
Progesterone directly abolished TNF-alpha-stimulated ET-1 and attenuated TNF-alpha-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.
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