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 H₂O₂ were higher in renal proximal tubule cells (RPTCs) from BALB/c than C57Bl/6J mice. High salt diet increased H₂O₂ production in kidneys from BALB/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H₂O₂ levels in BALB/c-RPTCs but not in C57Bl/6J-RPTCs. H₂O₂ (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 H₂O₂ production negatively regulates RPTC sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H₂O₂ production in renal proximal tubules, which would result in sodium retention and increased blood pressure.