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Renal medullary NAD(P)H‐oxidase subunit p67phox as a candidate gene in salt‐sensitive hypertension
Author(s) -
Feng Di,
Yang Chun,
Kurth Terry,
Liang Mingyu,
MorenoQuinn Carol,
Jacob Howard,
Cowley Allen W.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.791.6
Subject(s) - congenic , nad+ kinase , oxidase test , renal medulla , nad(p)h oxidase , endocrinology , strain (injury) , chemistry , microbiology and biotechnology , biology , medicine , biochemistry , gene , enzyme , kidney
There is great interest in better defining the genetic basis of salt‐sensitive hypertension (SSHT). We have generated a consomic strain (SS‐13BN/Mcwi) by introgression of the entire chr 13 of the normotensive Brown Norway rat into the Dahl salt‐sensitive SS/JRHsdMcwi (SS) genetic background. We also generated a congenic strain SS.BN‐(D13Rat151‐D13Rat197)/Mcwi introgressing a region of BN chr 13 and found both strains protected from SSHT. We previously found that renal medullary infusion of apocynin, an NAD(P)H oxidase inhibitor, partially blunted SSHT in the SS. p67phox(Ncf2), a gene located in the substituted region, encodes one of the cytosolic subunits of NAD(P)H oxidase. The mRNA and protein expression levels of p67phox and NAD(P)H oxidase activity in the outer medulla were significantly different between the SS and either SS‐13BN congenic or consomic on day 3 of high salt with no differences in mean arterial pressure (MAP) between these three strains. By day 7, MAP was significantly higher in the SS than the consomic or congenic strains and the difference in expression of p67phox was further enhanced. We conclude that the expression difference of p67phox determines the greater levels of NAD(P)H oxidase activity in SS rats compared to this congenic strain, and that p67phox is a viable candidate gene contributing to salt‐sensitive hypertension. Sequence variations are currently being evaluated. (HL‐827980)