Renal Hydrogen Peroxide Production Prevents Salt‐Sensitive Hypertension

Abstract

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 ( RPTC s) 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‐ RPTC s but not in C57Bl/6J‐ RPTC s. H 2 O 2 (10 μmol/L) treatment decreased sodium transport in RPTC s 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.