NADPH oxidase in the renal medulla causes oxidative stress and contributes to salt-sensitive hypertension in Dahl S rats

NE Taylor, P Glocka, M Liang, AW Cowley Jr - Hypertension, 2006 - Am Heart Assoc
NE Taylor, P Glocka, M Liang, AW Cowley Jr
Hypertension, 2006Am Heart Assoc
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 …
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 μg/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-13BN. 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.
Am Heart Assoc