Effects of 17-Hydroxyprogesterone on Tumor Necrosis Factor- -Induced Hypertension During Pregnancy

Abstract

BACKGROUND Inflammatory 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. METHODS TNF-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 treated+17-OHP. RESULTS Progesterone 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. CONCLUSION Progesterone 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.

Control of soluble fms-like tyrosine-1 (sFlt-1) production response to placental ischemia/hypoxia: role of tumor necrosis factor-α

“…To further assess the chronic interactions between of TNF-␣ and sFlt-1, we also examined the chronic effect of TNF-␣ infusion into NP rats on plasma sFlt-1 levels. Recombinant, purified rat TNF-␣ (BioSource International, Morrisville, NC) was infused via miniosmotic pump into NP rats at a rate of 50 ng/day for 5 days beginning on day 14 of gestation, as previously described by our laboratory (14,26). This rate of infusion is comparable to the increase in serum TNF-␣ in our RUPP model of placental ischemia (18).…”

“…Moreover, hypoxia stimulated a twofold increase in TNF-␣ (4) and sFlt-1 (27) from NP human placental explants. More recent data from our laboratory shows plasma and placental levels of sFlt-1 (11) and TNF-␣ (18) to be significantly elevated in response to reduced uterine perfusion pressure (RUPP) and TNF-␣-induced hypertension in pregnant rats (14). While these data suggest a link between the enhanced production of TNF-␣ and sFlt-1 in response to placental ischemia and/or hypoxia, the importance of TNF-␣ in stimulating sFlt-1 production is unknown.…”

Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage

“…After binding to the TNF-α receptor on the cell membrane of VECs, TNF-α exerts its biological effect via multiple pathways (11)(12)(13)(14)(15) to induce inflammation and alter coagulant/fibrinolytic function of VECs (16), leading to inflammation and coagulation. In the present study, a TNF-α-induced VEC injury model was established to investigate alterations in cell morphology and subcellular structures.…”

Effect of 17-α hydroxyprogesterone caproate on the production of tumor necrosis factor-α and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants

“…They further showed that in patients receiving 17-OHPC there was reduced cervical shortening. 14 Keiser et al 26 showed in a rat model that 17-OHPC attenuated the effect of TNF-a-induced hypertension by reducing the production of endothelin. Veillon et al 27 showed normalization of TNF-a and IL-6 in response to placental ischemia with the administration of 17-OHPC to rats.…”