Salt intake, oxidative stress, and renal expression of NADPH oxidase and superoxide dismutase.
The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF(2alpha) and malonyldialdehyde were measured in groups (n = 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH- and NADH-stimulated superoxide anion (O(2)(.-)) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally two- to threefold with salt intake (P < 0.001), whereas prostaglandin E(2) was unchanged. Renal cortical NADH- and NADPH-stimulable O(2)(.-) generation increased (P < 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P < 0.005) increased renal cortical mRNA expression of gp91(phox) and p47(phox) and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91(phox) and p47(phox) and decreased IC- and Mn-SOD. Thus, salt intake enhances generation of O(2)(.-) accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn-SOD.
Division of Nephrology and Hypertension and Cardiovascular-Kidney Institute, Georgetown University, Washington, DC 20007, USA.
Chagriya
C
Kitiyakara
Tina
T
Chabrashvili
Yifan
Y
Chen
Jonathan
J
Blau
Alex
A
Karber
Shakil
S
Aslam
William J
WJ
Welch
Christopher S
CS
Wilcox
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D023421:Models, Animal; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases