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

Item Type:Article
Title:Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension
Creators Name:Parrish, M.R., Wallace, K., Tam Tam, K.B., Herse, F., Weimer, A., Wenzel, K., Wallukat, G., Ray, L.F., Arany, M., Cockrell, K., Martin, J.N., Dechend, R. and Lamarca, B.
Abstract:Background: 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. Methods: 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. Results: 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. Conclusion: This study indicates that AT1-AA's contribute to placental oxidative stress; one mechanism whereby the AT1-AA mediates hypertension during pregnancy.
Keywords:Blood Pressure, Hypertension, Immune Activation, Oxidative Stress, Pregnancy, Animals, Rats
Source:American Journal of Hypertension
ISSN:0895-7061
Publisher:Nature Publishing Group
Volume:24
Number:7
Page Range:835-840
Date:July 2011
Official Publication:https://doi.org/10.1038/ajh.2011.62
PubMed:View item in PubMed

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