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


CONCLUSIONS
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.
Keiser
Sharon D
SD
Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Veillon
Edward W
EW
Parrish
Marc R
MR
Bennett
William
W
Cockrell
Kathy
K
Fournier
Lillian
L
Granger
Joey P
JP
Martin
James N
JN
Lamarca
Babbette
B
D019326:17-alpha-Hydroxyprogesterone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001795:Blood Pressure Determination; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000633:toxicity*
D000959:Antihypertensive Agents; D019332:Endothelin-1; D014409:Tumor Necrosis Factor-alpha; D019326:17-alpha-Hydroxyprogesterone