@article{5f213d9e9b7e47c6b45c820c4b22d4a0,
title = "Increased expression of NAD(P)H oxidase subunit p67phox in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension",
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, 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 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 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 p67 phox, we disrupted p67phox in SS rats using zinc-finger nucleases. 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.",
author = "Di Feng and Chun Yang and Geurts, {Aron M.} and Terry Kurth and Mingyu Liang and Jozef Lazar and Mattson, {David L.} and O'Connor, {Paul M.} and Cowley, {Allen W.}",
note = "Funding Information: The studies included in this manuscript are D.F.'s Ph.D. dissertation project. D.F., M.L., and A.W.C., Jr., designed the studies. A.M.G. used zinc-finger nucleases to generate the p67 phox−/− rat. D.F. and T.K. performed the phenotypic studies. D.F. and C.Y. carried out the molecular and cellular experiments. J.L. assisted with the sequencing studies. D.L.M. designed the respiratory burst experiment and P.M.O. performed this technique. D.F. analyzed all of the data. D.F. and A.W.C., Jr., wrote the manuscript. This work was supported by grants HL-82798 and HL-29587. We thank Meredith Skelton and Clark W. DuMontier for editing the manuscript. We thank Howard J. Jacob and Jaime Wendt Andrae for sequencing support. We thank Carol Moreno Quinn, Becky Schilling, Colin Hansen, Michael Grzybowski, and Jason Klotz for maintaining and genotyping the rat colonies. We thank Mike Flister and Chuanling Guo for technical assistance with respiratory burst experiments. We thank Yan Lu and Tao Wang (supported, in part, by grant 1UL1RR031973) for assistance with statistical analysis. We thank Lisa Henderson, Camille Torres, and Jenifer Phillips for assistance with protein and microalbumin measurements. We thank Glenn Slocum and Carol Bobrowitz for assistance with microscopic and histological analysis. ",
year = "2012",
month = feb,
day = "8",
doi = "10.1016/j.cmet.2012.01.003",
language = "English (US)",
volume = "15",
pages = "201--208",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}