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Autoantibodies to the angiotensin type I receptor in response to placental ischemia and tumor necrosis factor α in pregnant rats

Item Type:Article
Title:Autoantibodies to the angiotensin type I receptor in response to placental ischemia and tumor necrosis factor α in pregnant rats
Creators Name:Lamarca, B. and Wallukat, G. and Llinas, M. and Herse, F. and Dechend, R. and Granger, J.P.
Abstract:Circulating factors, such as agonistic autoantibodies to the angiotensin II type 1 (AT1) receptor (AT1-AAs), and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), are suggested to be important links between placental ischemia and hypertension in preeclamptic women. The purpose of this study was to determine the role of placental ischemia and TNF-alpha in stimulating the AT1-AA and the importance of AT1 receptor activation in mediating hypertension during reductions in uterine perfusion pressure (RUPP) and chronic TNF-alpha excess in pregnant rats. Increased mean arterial pressure in RUPP pregnant rats (122+/-1 mm Hg RUPP versus 101+/-1 mm Hg normal pregnant [NP]; P<0.001) was associated with increased circulating TNF-alpha (RUPP 48+/-13 pg/mL versus N 8+/-1 pg/mL; P<0.05) and AT1-AA (RUPP 15.3+/-1.6 U versus NP 0.6+/-0.3 U; P<0.001). Moreover, TNF-alpha-induced hypertension (97+/-2 to 112+/-2 mm Hg; P<0.05) in pregnant rats was associated with AT1-AA production (TNF-alpha rats 9.2+/-2.3 U versus NP rats 1.0+/-0.8 U; P<0.05). To determine the importance of AT1 receptor activation in mediating hypertension in RUPP- and TNF-alpha-treated rats, we administered an AT1 receptor antagonist to RUPP-, TNF-alpha-treated, and NP rats. Blood pressure responses were attenuated in RUPP rats (Delta 32 mm Hg versus Delta 20 mm Hg, NP; P<0.001), as well as in TNF-alpha-treated rats (Delta 10 mm Hg versus Delta 5 mm Hg, NP; P<0.05). Collectively, these data indicate that placental ischemia and TNF-alpha are important stimuli of AT1-AA, and activation of the AT1 receptor appears to, in part, mediate hypertension produced by RUPP and TNF-alpha in pregnant rats.
Keywords:Pregnancy, Inflammatory Cytokines, Hypertension, AT1 Receptor Activation, Autoantibodies, Animals, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:52
Number:6
Page Range:1168-1172
Date:December 2008
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.108.120576
PubMed:View item in PubMed

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