Faculty Collaboration Database

NADPH oxidase in the renal medulla causes oxidative stress and contributes to salt-sensitive hypertension in Dahl S rats. Hypertension 2006 Apr;47(4):692-8

Date

03/01/2006

Pubmed ID

16505210

DOI

10.1161/01.HYP.0000203161.02046.8d

Scopus ID

2-s2.0-33645832749 (requires institutional sign-in at Scopus site)   173 Citations

Abstract

Dahl salt-sensitive (SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt-sensitivity compared with consomic, salt-resistant SS-13BN 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-13BN 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-13BN 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-13BN 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 microg/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.

Author List

Taylor NE, Glocka P, Liang M, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

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

Acetophenones
Animals
Catalase
Chromosomes, Mammalian
Drug Resistance
Enzyme Inhibitors
Glutathione Peroxidase
Hypertension
Isoenzymes
Kidney Medulla
NADPH Oxidases
Oxidative Stress
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sodium Chloride, Dietary
Superoxide Dismutase
Superoxides