on November 3, 2008
Published online before print November 3, 2008, doi: 10.1161/HYPERTENSIONAHA.108.120881
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Submitted on August 1, 2008
From the Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson. * To whom correspondence should be addressed. E-mail: jgranger{at}physiology.umsmed.edu.
Abstract—Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-
Revised on August 29, 2008
Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats. Effect of Tumor Necrosis Factor-
Babbette LaMarca; 
Blockade
(TNF-). This study was designed to determine the role of endogenous TNF- 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-–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- 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- 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- 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- is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy.
Key words: hypertension • pregnancy • inflammation • cytokines • endothelial activation
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