To determine mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc). After weaning, male rats were treated for 2 wks with: vehicle + normal sodium diet (0.4%, CON-NS), vehicle + high sodium diet (4%, CON-HS), CAP-NS, and CAP-HS. Systolic blood pressure increased significantly in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F₂ levels increased in CAP-HS and CON-HS, and were higher in CAP-HS vs CON-HS rats (p<0.05). Superoxide (O₂) levels in the renal cortex and medulla increased by ~ 45% in CAP-HS, which was prevented by a selective NAD(P)H oxidase inhibitor apocynin. Expression of NAD(P)H oxidase subunits including p47^phox and gp91^phox in the cortex and medulla increased significantly in CAP-HS (p<0.05). In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD increased significantly in the medulla in CAP-HS and CON-HS but in the cortex in CAP-HS only. Creatinine clearance decreased by ~ 45% in CAP-HS, which correlated with O₂levels in the renal cortex (r = -0.76; p<0.001). Therefore, regardless of compensatory enhancement of SOD activities, increased renal oxidative stress in CAP-HS rats is likely the result of increased expression and activities of NAD(P)H oxidase, and may contribute to decreased renal function and increased blood pressure. Our data suggest that sensory nerves play a compensatory role in attenuating renal oxidative stress during HS intake.