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(Hypertension. 2008;52:1168.)
© 2008 American Heart Association, Inc.

Original Articles

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

Babbette LaMarca; Gerd Wallukat; Mayte Llinas; Florian Herse; Ralf Dechend; Joey P. Granger

From the Department of Physiology (B.L., M.L., J.P.G.), University of Mississippi Medical Center, Jackson; and HELIOS Clinic (G.W., F.H., R.D.), Charite, Campus-Buch and Max-Delbrueck Center, Berlin, Germany.

Correspondence to Joey P. Granger, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail jgranger{at}physiology.umsmed.edu

Circulating factors, such as agonistic autoantibodies to the angiotensin II type 1 (AT1) receptor (AT1-AAs), and inflammatory cytokines, including tumor necrosis factor (TNF-), 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- 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- 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- (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-–induced hypertension (97±2 to 112±2 mm Hg; P<0.05) in pregnant rats was associated with AT1-AA production (TNF- 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-–treated rats, we administered an AT1 receptor antagonist to RUPP–, TNF-–treated, and NP rats. Blood pressure responses were attenuated in RUPP rats ( 32 mm Hg versus 20 mm Hg, NP; P<0.001), as well as in TNF-–treated rats ( 10 mm Hg versus 5 mm Hg, NP; P<0.05). Collectively, these data indicate that placental ischemia and TNF- are important stimuli of AT1-AA, and activation of the AT1 receptor appears to, in part, mediate hypertension produced by RUPP and TNF- in pregnant rats.

Key Words: pregnancy • inflammatory cytokines • hypertension • AT1 receptor activation • autoantibodies

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