Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Abstract

ABSTRACT. 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 PGF2αand 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 (O2·−) 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 E2was unchanged. Renal cortical NADH- and NADPH-stimulable O2·−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 gp91phoxand p47phoxand 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 gp91phoxand p47phoxand decreased IC- and Mn-SOD. Thus, salt intake enhances generation of O2·−accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn-SOD. E-mail: wilcoxch@georgetown.edu