Enhanced atherosclerosis and kidney dysfunction in eNOS-/-Apo-/- mice are ameliorated by enalapril treatment
Enhanced atherosclerosis and kidney dysfunction in eNOS-/-Apo-/- mice are ameliorated by enalapril treatment
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DOI：
10.1172/jci8376
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发表时间：
2000-02-01
影响因子：
15.9
通讯作者：
Maeda, N
中科院分区：
文献类型：
--
作者：
Knowles, JW;Reddick, RL;Maeda, N
高血压和动脉粥样硬化是发达国家发病率和死亡率的重要原因。我们研究了这些条件之间的相互作用，通过饲养小鼠动脉粥样硬化，由于缺乏载脂蛋白（apo）E与小鼠高血压，由于缺乏内皮型一氧化氮合酶（eNOS）。与血压正常但动脉粥样硬化（NNee）小鼠相比，双缺陷小鼠（NNee）具有更高的血压（BP）和增加的动脉粥样硬化病变大小，但血浆脂蛋白谱没有变化。nnee小鼠还发生肾损伤，表现为血浆肌酐升高、肾重/体重比降低以及肾小球脂质沉积和钙化。依那普利治疗消除了eNOS缺乏对nnee小鼠血压、动脉粥样硬化和肾功能障碍的有害影响。与此形成鲜明对比的是，在Apoe（-/-）小鼠中，诱导型NOS的遗传缺乏（不影响BP）对动脉粥样硬化病变的发展没有影响。我们还观察到血压和动脉粥样硬化病变的大小呈正相关。这些结果表明，eNOS缺乏的致动脉粥样硬化作用可以部分解释为血压升高，并再次强调控制高血压在预防动脉粥样硬化中的重要性。
Hypertension and atherosclerosis are each important causes of morbidity and mortality in the developed world. We have investigated the interaction between these conditions by breeding mice that are atherosclerotic due to lack of apolipoprotein (apo) E with mice that are hypertensive due to lack of endothelial nitric oxide synthase (eNOS). The doubly deficient mice (nnee) have higher blood pressure (BP) and increased atherosclerotic lesion size but no change in plasma lipoprotein profiles compared with normotensive but atherosclerotic (NNee) mice. The nnee mice also develop kidney damage, evidenced by increased plasma creatinine, decreased kidney weight/body weight ratio, and glomerular lipid deposition and calcification. Enalapril treatment abolishes the deleterious effects of eNOS deficiency on BP, atherosclerosis, and kidney dysfunction in nnee mice. In striking contrast, a genetic lack of inducible NOS, which does not affect BP, has no effect on the development of atherosclerotic lesions in Apoe(-/-) mice. We also observed a positive relationship between BP and size of atherosclerotic lesions. These results suggest that the atherogenic effects of eNOS deficiency can be partially explained by an increase in BP and reemphasize the importance of controlling hypertension in preventing atherosclerosis.