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

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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

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NADPH Oxidase
Oxidative Stress
Salts
Hypertension
Kidney
neutrophil cytosol factor 67K
Inbred Dahl Rats
Renal Hypertension
Zinc Fingers
Genetic Promoter Regions
Animal Models
Alleles
Diet

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Increased expression of NAD(P)H oxidase subunit p67 phox in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension. / Feng, Di; Yang, Chun; Geurts, Aron M.; Kurth, Terry; Liang, Mingyu; Lazar, Jozef; Mattson, David L.; O'Connor, Paul M; Cowley, Allen W.

In: Cell Metabolism, Vol. 15, No. 2, 08.02.2012, p. 201-208.

Research output: Contribution to journalArticle

Feng, Di ; Yang, Chun ; Geurts, Aron M. ; Kurth, Terry ; Liang, Mingyu ; Lazar, Jozef ; Mattson, David L. ; O'Connor, Paul M ; Cowley, Allen W. / Increased expression of NAD(P)H oxidase subunit p67 phox in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension. In: Cell Metabolism. 2012 ; Vol. 15, No. 2. pp. 201-208.
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AU - Liang, Mingyu

AU - Lazar, Jozef

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