Increased expression of NAD(P)H oxidase subunit p67(phox) in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension.
Increased expression of NAD(P)H oxidase subunit p67(phox) in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension.
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DOI：
10.1016/j.cmet.2012.01.003
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发表时间：
2012-02-08
期刊：
影响因子：
29
通讯作者：
Cowley AW Jr
中科院分区：
文献类型：
--
作者：
Feng D;Yang C;Geurts AM;Kurth T;Liang M;Lazar J;Mattson DL;O'Connor PM;Cowley AW Jr
NAD(P)H氧化酶在盐敏感型高血压的发生发展中起重要作用。在此，我们发现在人类盐敏感性高血压的动物模型Dahl盐敏感(SS)大鼠的外肾髓质中，NAD(P)H氧化酶的一个亚单位p67Phox的表达随着高盐饮食的反应而增加。与耐盐品系相比，SS大鼠的NAD(P)H氧化酶活性和对盐的敏感性与p67Phox的高表达有关，而与观察到的其他亚基无关。P67Phox的SS等位基因在启动子区域发生了遗传突变，导致启动子活性高于耐盐菌株。为了验证p67Phox的重要性，我们利用锌指核酸酶技术对SS大鼠的p67Phox进行了阻断。这些大鼠表现出盐敏感型高血压和肾髓质氧化应激和损伤的显着减少。P67Phox可能是盐敏感型高血压治疗的靶点。
NAD(P)H oxidase has been shown to be important in the development of salt-sensitive hypertension. Here we show that the expression of a subunit of NAD(P)H oxidase, p67phox, was increased in response to a high salt diet in the outer renal medulla of the Dahl salt-sensitive (SS) rat, an animal model for human salt-sensitive hypertension. The higher expression of p67phox, not the other subunits observed, was associated with higher NAD(P)H oxidase activity and salt-sensitivity in SS rats compared with a salt-resistant strain. Genetic mutations of the SS allele of p67phox were found in the promoter region and contributed to higher promoter activity than that of the salt-resistant strain. To verify the importance of p67phox, we disrupted p67phox in SS rats using zinc finger nucleases technology. These rats exhibited a significant reduction of salt-sensitive hypertension and renal medullary oxidative stress and injury. p67phox could represent a target for salt-sensitive hypertension therapy.
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