Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats Effect of Tumor Necrosis Factor-α Blockade

被引：133

作者：

LaMarca, Babbette ^{[1
]}

Speed, Josh ^{[1
]}

Fournier, Lillian ^{[1
]}

Babcock, Sara A. ^{[1
]}

Berry, Hunter ^{[1
]}

Cockrell, Kathy ^{[1
]}

Granger, Joey P. ^{[1
]}

机构：

[1] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Ctr Excellence Cardiovasc Renal Res, Jackson, MS 39216 USA

来源：

HYPERTENSION | 2008年 / 52卷 / 06期

基金：

美国国家卫生研究院;

关键词：

hypertension; pregnancy; inflammation; cytokines; endothelial activation;

D O I：

10.1161/HYPERTENSIONAHA.108.120881

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-alpha (TNF-alpha). This study was designed to determine the role of endogenous TNF-alpha 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-alpha-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-alpha 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-alpha 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-alpha 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-alpha is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy. (Hypertension. 2008;52:1161-1167.)

引用

页码：1161 / 1167

页数：7

共 29 条

[1]

Agirbasli M, 2006, CLIN EXP RHEUMATOL, V24, P580

[2] Endothelin type A receptor blockade attenuates the hypertension in response to chronic reductions in uterine perfusion pressure [J].