Autoantibodies to the Angiotensin Type I Receptor in Response to Placental Ischemia and Tumor Necrosis Factor α in Pregnant Rats

Abstract

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 P P P P P 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.