期刊
HYPERTENSION
卷 47, 期 4, 页码 692-698出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000203161.02046.8d
关键词
oxidative stress; hypertension, renal; renal disease; sodium; antioxidants
资金
- NHLBI NIH HHS [HL-29587, HL-54998, HL-077263] Funding Source: Medline
Dahl salt-sensitive ( SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt-sensitivity compared with consomic, salt-resistant SS-13(BN) rats, despite highly similar genetic backgrounds. The present study examined potential sources of renal medullary superoxide in prehypertensive SS rats fed a 0.4% NaCl diet by assessing activity and protein levels of superoxide producing and scavenging enzymes. Superoxide production was nearly doubled in SS rats compared with SS-13(BN) rats as determined by urinary 8-isoprostane excretion and renal medullary oxy-ethidium microdialysate levels. Medullary superoxide production in tissue homogenates was greater in SS rats, and the NADPH oxidase inhibitor diphenylene iodonium preferentially reduced SS levels to those found in SS-13(BN) rats. Dinitrophenol, a mitochondrial uncoupler, eliminated the remaining superoxide production in both strains, whereas inhibition of xanthine oxidase, NO synthase, and cycloxygenase had no effect. L-arginine, NO synthase, superoxide dismutase, catalase, and glutathione peroxidase activities between SS and SS-13(BN) rats did not differ. Chronic blood pressure responses to a 4% NaCl diet were then determined in the presence or absence of the NADPH oxidase inhibitor apocynin ( 3.5 mu g/kg per minute), chronically delivered directly into the renal medulla. Apocynin infusion reduced renal medullary interstitial superoxide from 1059 +/- 130 to 422 +/- 80 ( oxyethidium fluorescence units) and mean arterial pressure from 175 +/- 4 to 157 +/- 6 mm Hg in SS rats, whereas no effects on either were observed in the SS-13(BN). We conclude that excess renal medullary superoxide production in SS rats contributes to salt-induced hypertension, and NADPH oxidase is the major source of the excess superoxide.
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