Renal Hydrogen Peroxide Production Prevents Salt‐Sensitive Hypertension

BACKGROUND: The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and BALB/c mice have different blood pressure sensitivities to salt intake. High salt intake increases blood pressure in some C57Bl/6J mouse strains but not in any BALB/c mouse strain. METHODS AND RESULTS: We determined the cause of the difference in salt sensitivity between C57Bl/6 and BALB/c mice. Basal levels of superoxide and H(2)O(2) were higher in renal proximal tubule cells (RPTCs) from BALB/c than C57Bl/6J mice. High salt diet increased H(2)O(2) production in kidneys from BALB/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H(2)O(2) levels in BALB/c‐RPTCs but not in C57Bl/6J‐RPTCs. H(2)O(2) (10 μmol/L) treatment decreased sodium transport in RPTCs from BALB/c but not C57Bl/6J mice. Overexpression of catalase in the mouse kidney predisposed BALB/c mice to salt‐sensitive hypertension. CONCLUSIONS: Our data show that the level of salt‐induced H(2)O(2) production negatively regulates RPTC sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H(2)O(2) production in renal proximal tubules, which would result in sodium retention and increased blood pressure.