Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy.
Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy.
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DOI：
10.1161/hypertensionaha.113.01648
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
Lamarca B
中科院分区：
文献类型：
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作者：
Brewer J;Liu R;Lu Y;Scott J;Wallace K;Wallukat G;Moseley J;Herse F;Dechend R;Martin JN Jr;Lamarca B
先兆子痫期间的高血压与母体血管对血管紧张素II（ANGII）的敏感性增加有关。本研究旨在确定妊娠期间ANGII I型受体（AT 1-AA）的激动性自身抗体增强血压（MAP）和肾血管对ANGII敏感性的机制。首先，我们检查了MAP和肾动脉阻力指数（RARI）在妊娠大鼠中与对照妊娠大鼠相比，长期给予ANGII或AT 1-AA或AT 1-AA+ANGII的反应。为了研究妊娠期间响应于AT 1-AA的敏感性提高的机制，我们研究了内源性ANGII在输注AT 1-AA的妊娠大鼠中的作用，以及AT 1-AA+ANGII处理的大鼠中内皮素-1和氧化应激的作用。慢性ANGII使NP大鼠的MAP从95 +/-2增加到115 +/-2 mmHg。慢性AT 1-AA使NP大鼠的MAP增加至118+/−1 mmHg，AT 1-AA+ANGII进一步增加至123+/−2。在AT 1-AA预处理的血管中，ANGII从（10−11-10−8）增加使Af-Art直径减小15-20%，但使Af-Art直径急剧减小60%。RARI从NP大鼠的0.67增加到AT 1-AA输注的0.70，在AT 1-AA + ANGII输注的大鼠中加剧到0.74。依那普利可降低AT 1-AA诱导的高血压，但未减弱。与单独的AT 1-AA相比，AT 1-AA+ANGII增加了组织ET-1和ROS，并且阻断这些途径中的任一个对MAP或RARI具有显著影响。这些数据支持这样的假设，即AT 1-AA，通过激活ET-1和氧化应激和与内源性ANGII的相互作用，是重要的机制，从而MAP和肾血管反应在先兆子痫期间增强。
Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (MAP) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index (RARI) in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared to control pregnant rats. In order to examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy we examined the role of endogenous ANGII in AT1-AA infused pregnant rats, Endothelin-1 and oxidative stress in AT1-AA+ANGII treated rats. Chronic ANGII increased MAP from 95 +/−2 in NP rats to 115 +/−2 mmHg. Chronic AT1-AA increased MAP to 118+/−1 mmHg in NP rats which further increased to 123+/−2 with AT1-AA+ANGII. Increasing ANGII from (10−11-10−8) decreased Af-Art diameter 15-20% but sharply decreased Af-Art diameter 60% in AT1-AA pretreated vessels. RARI increased from 0.67 in NP rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA + ANGII infused rats. AT1-AA-induced hypertension decreased with Enalapril but was not attenuated. Both tissue ET-1 and ROS increased with AT1-AA+ANGII compared to AT1-AA alone and blockade of either of these pathways had significant effects on MAP or RARI. These data support the hypothesis that AT1-AA, via activation of ET-1 and oxidative stress and interaction with endogenous ANGII, are important mechanisms whereby MAP and renal vascular responses are enhanced during preeclampsia.