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The contribution of renal medullary NADPH oxidase and mitochondrial superoxide production to salt‐induced hypertension in Dahl S rats.
Author(s) -
Taylor Norman E.,
Glocka Padden,
Liang Mingyu,
Cowley Allen W.
Publication year - 2006
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.20.4.a724-d
Subject(s) - endocrinology , medicine , chemistry , apocynin , nadph oxidase , xanthine oxidase , superoxide , superoxide dismutase , renal medulla , catalase , kidney , oxidative stress , biochemistry , enzyme , biology
Dahl salt‐sensitive (SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt‐sensitivity compared to consomic, salt‐resistant SS‐13 BN rats, despite highly similar genetic backgrounds. The present study examined potential sources of renal medullary superoxide (O 2 − ) in prehypertensive SS rats fed a 0.4% NaCl diet, by assessing activity and protein levels of O 2 − producing and scavenging enzymes. O 2 − production was increased 2X in SS rats vs. SS‐13 BN rats as determined by urinary 8‐isoprostane excretion and renal medullary oxy‐ethidium microdialysate levels. Inhibition of NADPH oxidase preferentially reduced levels to those found in SS‐13 BN rats. ‐Dinitrophenol, a mitochondrial uncoupler, eliminated the remaining O 2 production in both strains, while inhibition of xanthine oxidase, nitric oxide synthase, and cycloxygenase had no effect. L‐arginine, NOS, superoxide dismutase, catalase and glutathione peroxidase activities between SS and SS‐13 BN rats did not differ. Blood pressure responses to a 4% NaCl diet were then determined in the presence or absence of the NADPH oxidase inhibitor, apocynin (3.5μg/kg/min), chronically delivered directly into the renal medulla. Renal medullary interstitial O 2 − was reduced from 1059±130 to 422±80 (oxy‐ethidium fluorescence units) and mean arterial pressure from 175±4 to 157±6 mmHg in SS rats only. We conclude that excess renal medullary O 2 − production in SS rats contributes to salt‐induced hypertension and NADPH oxidase is the major source of the excess O 2 − . (NIH‐NHLBI HL‐29587, HL‐54998, HL‐077263; AHA‐04100437)