Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species
Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species
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DOI：
10.1016/j.atherosclerosis.2006.11.030
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发表时间：
2007-11-01
期刊：
影响因子：
5.3
通讯作者：
Taylor, W. Robert
中科院分区：
文献类型：
--
作者：
Doran, Derek E.;Weiss, Daiana;Taylor, W. Robert
血管紧张素II受体阻断已在几种不同的动物模型中显示出可抑制动脉粥样硬化。我们试图确定这种效应是血压本身降低的结果，还是受体阻断的抗炎作用的结果。载脂蛋白E缺陷型小鼠被喂食高脂肪饮食，并分别用血管紧张素II受体拮抗剂坎地沙坦（0.5毫克/千克/天，皮下注射）或钙通道阻滞剂氨氯地平（7.5毫克/千克/天，与食物混合）进行治疗。对动脉粥样硬化病变面积、主动脉炎症基因表达以及主动脉过氧化氢和超氧化物的产生进行了检测。我们发现，尽管血压降低程度相似，但坎地沙坦而非氨氯地平治疗显著减缓了动脉粥样硬化的发展。同样，坎地沙坦治疗抑制了主动脉炎症基因的表达和活性氧的产生，而氨氯地平没有这些作用。这些数据表明，血管紧张素II受体阻断通过减少血管氧化应激和炎症基因的产生来抑制动脉粥样硬化，这一作用与血压降低无关。（c）2006爱思唯尔爱尔兰有限公司。保留所有权利。
Angiotensin 11 receptor blockade has been shown to inhibit atherosclerosis in several different animal models. We sought to determine if this effect was the result of blood pressure reduction per se or a result of the anti-inflammatory effects of receptor blockade. ApoE-deficient mice were fed a high fat diet and treated with either an angiotensin II receptor antagonist, candesartan (0.5 mg/kg/day, SC) or a calcium channel blocker, amlodipine (7.5 mg/kg/day, mixed with food). Atherosclerotic lesion area, aortic inflammatory gene expression as well as aortic H2O2 and superoxide production were assayed. We found that candesartan but not amlodipine treatment dramatically attenuated the development of atherosclerosis despite a similar reduction in blood pressure. Similarly, candesartan treatment inhibited aortic expression of inflammatory genes and production of reactive oxygen species, effects not seen with amlodipine. These data demonstrate that angiotensin II receptor blockade inhibits atherosclerosis by reducing vascular oxidative stress and inflammatory gene production independent of blood pressure reduction. (c) 2006 Elsevier Ireland Ltd. All rights reserved.