Increased expression of NAD(P)H oxidase subunit p67 phox in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension

Di Feng, Chun Yang, Aron M. Geurts, Terry Kurth, Mingyu Liang, Jozef Lazar, David L. Mattson, Paul M. O'Connor, Allen W. Cowley

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)201-208
Number of pages8
JournalCell Metabolism
Volume15
Issue number2
DOIs
StatePublished - Feb 8 2012

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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