Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Am J Hypertens. 2011 Jul;24(7):835-40. doi: 10.1038/ajh.2011.62. Epub 2011 Apr 7.
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.
血管紧张素 II 型 1 型受体（AT1-AA）的激动性自身抗体和活性氧（ROS）与子痫前期的病理生理学有关。本研究的目的是确定 AT1-AA 刺激体内胎盘氧化应激的作用以及 ROS 在介导怀孕期间对 AT1-AA 反应性高血压中的作用。
为了实现这些目标，在存在和不存在超氧化物歧化酶类似物（tempol）的情况下，分析 AT1-AA 诱导的高血压妊娠大鼠的血压（平均动脉压（MAP））和 ROS。从妊娠第 12 天开始，向妊娠大鼠给予大鼠 AT1-AA（1:50）和 tempol（30mg/kg/天）。在第 19 天，分析 MAP 并通过鲁米诺化学发光法收集组织以进行 ROS 分析。
MAP 从正常妊娠（NP）大鼠的 101±2mmHg 增加到慢性 AT1-AA 输注大鼠的 116±2mmHg（P=0.002）。NP 大鼠胎盘基础和 NADPH 氧化酶刺激的 ROS 分别为 29±6 和 92±10 相对光单位（RLUs）。这些水平增加到 AT1-AA 输注大鼠的 159±29（P<0.0001）和 287±60RLUs（P<0.006）。AT1-AA+tempol 大鼠的 MAP 为 109±2mmHg，与 tempol 治疗对照组（109±3mmHg）无差异。在 AT1-AA 治疗大鼠中，tempol 降低了基础和 NADPH 刺激的胎盘 ROS（121±13；262±21RLUs）。tempol 治疗对照组的基础和 NADPH 刺激的 ROS 分别为 69±24；141±33RLUs。
本研究表明，AT1-AA 有助于胎盘氧化应激；AT1-AA 介导怀孕期间高血压的一种机制。
