Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats
Effect of Tumor Necrosis Factor-α Blockade
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-α (TNF-α). This study was designed to determine the role of endogenous TNF-α in mediating changes in arterial pressure and endothelin-1 (ET-1) in RUPP rats. To achieve this goal we examined the effect of RUPP in the presence and absence of a TNF-α-soluble receptor, etanerecept (0.4 mg/kg). Mean arterial pressure increased from 102±1 mm Hg in normal pregnant (NP) rats to 134±3 mm Hg (P<0.05) in RUPP rats. Serum TNF-α increased to 40±7.6 pg/mL in RUPP rats (n=24) versus 14.8±3.3 pg/mL (n=16; P<0.05) in NP rats. Administration of etanerecept decreased TNF-α in RUPP rats (n=20) to 17.2±3 pg/mL and mean arterial pressure to 118±2 mm Hg (P<0.05). Tissue ET-1 decreased in etanerecept-treated RUPP rats compared with control RUPP rats. The direct effect of TNF-α blockade on endothelial activation in response to placental ischemia was examined in human umbilical vein endothelial cells. ET-1 secreted from human umbilical vein endothelial cells treated with RUPP serum was 59.2+16 pg/mg and decreased when etanerecept was added to the medium with RUPP serum (7.60±0.77 pg/mg), as well as in response to serum from etanerecept-treated RUPP rats (7.30±0.55 pg/mg; P<0.001). ET-1 secreted from human umbilical vein endothelial cells was 15.6±2 pg/mg when treated with NP serum. These data support the hypothesis that endogenous TNF-α is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy.
- Received August 1, 2008.
- Revision received August 29, 2008.
- Accepted October 8, 2008.