Increased Expression of NAD(P)H Oxidase Subunit p67phox in the Renal Medulla Contributes to Excess Oxidative Stress and Salt-Sensitive Hypertension

被引:125
作者
Feng, Di [1 ]
Yang, Chun [1 ]
Geurts, Aron M. [2 ,3 ]
Kurth, Terry [1 ]
Liang, Mingyu [1 ]
Lazar, Jozef [2 ]
Mattson, David L. [1 ]
O'Connor, Paul M. [1 ]
Cowley, Allen W., Jr. [1 ,3 ]
机构
[1] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
[2] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Ctr Cardiovasc, Milwaukee, WI 53226 USA
关键词
NADPH OXIDASES; PERFUSION-PRESSURE; NITRIC-OXIDE; T-LYMPHOCYTES; SUPEROXIDE; KIDNEY; ACTIVATION; PROTECTION; INJURY; RATS;
D O I
10.1016/j.cmet.2012.01.003
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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, p67(phox), 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 p67(phox), 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 p67(phox) were found in the promoter region and contributed to higher promoter activity than that of the salt-resistant strain. To verify the importance of p67(phox), we disrupted p67(phox) in SS rats using zinc-finger nucleases. These rats exhibited a significant reduction of salt-sensitive hypertension and renal medullary oxidative stress and injury. p67(phox) could represent a target for salt-sensitive hypertension therapy.
引用
收藏
页码:201 / 208
页数:8
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