Browsing by Subject "AT1 receptor activation"

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    Autoantibodies to the Angiotensin Type I Receptor in Response to Placental Ischemia and Tumor Necrosis Factor α in Pregnant Rats
    (American Heart Association, 2008-10-13) LaMarca, Babbette; Wallukat, Gerd; Llinas, Maria Teresa; Herse, Florian; Dechend, Ralf; Granger, Joey P.; Fisiología
    Circulating factors, such as agonistic autoantibodies to the angiotensin II type 1 (AT1) receptor (AT1-AAs), and inflammatory cytokines, including tumor necrosis factor α (TNF-α), 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-α 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-α 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-α (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-α–induced hypertension (97±2 to 112±2 mm Hg; P<0.05) in pregnant rats was associated with AT1-AA production (TNF-α 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-α–treated rats, we administered an AT1 receptor antagonist to RUPP–, TNF-α–treated, and NP rats. Blood pressure responses were attenuated in RUPP rats (Δ 32 mm Hg versus Δ 20 mm Hg, NP; P<0.001), as well as in TNF-α–treated rats (Δ 10 mm Hg versus Δ 5 mm Hg, NP; P<0.05). Collectively, these data indicate that placental ischemia and TNF-α are important stimuli of AT1-AA, and activation of the AT1 receptor appears to, in part, mediate hypertension produced by RUPP and TNF-α in pregnant rats.