Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension.

Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi, USA.

American journal of hypertension 2011 Jul

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Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and reactive oxygen species (ROS) are implicated in the pathophysiology of preeclampsia. The objective of this study was to determine the role of AT1-AA to stimulate placental oxidative stress in vivo and role ROS in mediating hypertension in response to AT1-AA during pregnancy. To achieve these goals, blood pressure (mean arterial pressure (MAP)) and ROS were analyzed in AT1-AA-induced hypertensive pregnant rats in the presence and absence of a superoxide dismutase mimetic, tempol. Rat AT1-AA (1:50) and tempol (30 mg/kg/day) were administered to pregnant rats beginning on day 12 of gestation. On day 19, MAP was analyzed and tissues collected for ROS analysis via lucigenin chemiluminescence. MAP increased from 101 ± 2 normal pregnant (NP) rats to 116 ± 2 mm Hg in chronic AT1-AA infused rats (P = 0.002). Placental basal and NADPH oxidase stimulated ROS was 29 ± 6 and 92 ± 10 relative light units (RLUs) in NP rats. These levels increased to 159 ± 29 (P < 0.0001) and 287 ± 60 RLUs (P < 0.006) in AT1-AA infused rats. MAP in AT1-AA + tempol rats was 109 ± 2 mm Hg, no difference than tempol-treated controls (109 ± 3 mm Hg). Administration of tempol decreased basal and NADPH-stimulated placental ROS in AT1-AA-treated rats (121 ± 13; 262 ± 21 RLUs). Basal and NADPH-stimulated ROS in tempol-treated controls were 69 ± 24; 141 ± 33 RLUs. This study indicates that AT1-AA's contribute to placental oxidative stress; one mechanism whereby the AT1-AA mediates hypertension during pregnancy.

Citation

Marc R Parrish, Kedra Wallace, Kiran B Tam Tam, Florian Herse, Abram Weimer, Katrin Wenzel, Gerd Wallukat, Lillian F Ray, Marrietta Arany, Kathy Cockrell, James N Martin, Ralf Dechend, Babbette LaMarca. Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension. American journal of hypertension. 2011 Jul;24(7):835-40