Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

Abstract

To determine the 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) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F2αlevels increased by ∼40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet ( P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O2−·) levels in the renal cortex and medulla increased by ∼45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats ( P < 0.05). Enhanced O2−· levels in the cortex and medulla in CAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47phoxand gp91phoxin the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by ∼45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats ( P < 0.05). O2−· levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance ( r = −0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.