Helmholtz Gemeinschaft


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. and Wallace, K. and Tam Tam, K.B. and Herse, F. and Weimer, A. and Wenzel, K. and Wallukat, G. and Ray, L.F. and Arany, M. and Cockrell, K. and Martin, J.N. and 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
Publisher:Nature Publishing Group
Page Range:835-840
Date:July 2011
Official Publication:https://doi.org/10.1038/ajh.2011.62
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library