血管紧张素Ⅱ AT1 受体自身抗体致高血压：活性氧在妊娠高血压中的作用。
Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension.
机构信息
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
出版信息
Am J Hypertens. 2011 Jul;24(7):835-40. doi: 10.1038/ajh.2011.62. Epub 2011 Apr 7.
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.
背景
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。
方法
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。
结果
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。
结论
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。
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