Renal medullary NADPH oxidase activity in DOCA‐salt hypertensive rats

Both endothelin-1 (ET-1) and oxidative stress are elevated in experimental forms of hypertension. We hypothesized that DOCA salt hypertension increases ET-1 which stimulates NADPH oxidase in the kidney. Four groups of rats were studied for a period of 3 weeks; placebo, DOCA (200 mg; subcutaneous), DOCA + the ETA receptor antagonist, ABT-627 (10–30 mg/kg/day), and DOCA + the nonspecific vasodilator, hydralazine (HYD) (10–15 mg/kg/day). ABT and HYD treated rats had lower mean arterial pressures (149 ± 12 and 139 ± 15 mmHg, respectively) than DOCA (174 ± 12 mmHg, p<0.05) as measured by telemetry. Protein excretion was increased in DOCA rats (103 ± 16 mg/day) and ABT (104 ± 41 mg/day) compared to placebo (22 ± 6 mg/day, p<0.05) and HYD (37 ± 13 mg/day, p<0.05). There was no difference in NADPH oxidase activity, determined by lucigenin chemiluminescence, in the renal cortex between placebo and DOCA groups. Renal inner medullary NADPH oxidase activity was increased in DOCA, ABT, and HYD compared to placebo (17.3 ± 1.3, 17.0 ± 1.1, 16.2 ± 0.2, 9.8 ± 1.7 cpm/μg, respectively, p<0.05). These data indicate that increased inner medullary NADPH oxidase activity and increased protein excretion in DOCA is independent of ET-1. Funded by HL60653, HL64776 and AHA0340113N.