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Increased expression of NAD(P)H oxidase subunit p67(phox) in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension. Cell Metab 2012 Feb 08;15(2):201-8

Date

02/14/2012

Pubmed ID

22326221

Pubmed Central ID

PMC3280886

DOI

10.1016/j.cmet.2012.01.003

Scopus ID

2-s2.0-84863012892   103 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.

Author List

Feng D, Yang C, Geurts AM, Kurth T, Liang M, Lazar J, Mattson DL, O'Connor PM, Cowley AW Jr

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Vice Chair, Center Director, Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Base Sequence
Blood Pressure
Blotting, Western
DNA Primers
Hypertension
Kidney Medulla
Molecular Sequence Data
Mutation
Oxidative Stress
Phosphoproteins
Rats
Rats, Inbred Dahl
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA