Inhibition of Na+ channel or Na+/H+ exchanger attenuates the hydrogen peroxide-induced derangements in isolated perfused rat heart

The effect of tetrodotoxin, a specific inhibitor of the Na+ channel, and 5- (N,N-dimethyl)amiloride, a specific inhibitor of the Na+/H+ exchanger, on t he mechanical and metabolic derangements induced by hydrogen peroxide (H2O2 ) was studied in the isolated perfused rat heart. The isolated rat heart wa s perfused aerobically at a constant how rate and driven electrically. H2O2 (600 mu M) decreased the left ventricular developed pressure and incre ased the left ventricular end-diastolic pressure (i.e. mechanical dysfuncti on), decreased the tissue levels of adenosine triphosphate and adenosine di phosphate (i.e. metabolic derangement), and increased the tissue level of m alondialdehyde (i.e. lipid]peroxidation). These mechanical and metabolic de rangements induced by H2O2 were significantly attenuated by tetrodotoxin (3 mu M) or 5-(N,N-dimethyl)-amiloride (15 mu M). Neither tetrodotoxin nor 5- (N,N-dimethyl)-amiloride modified the tissue malondialdehyde level, which w as increased by H2O2 In the normal (H2O2-untreated) heart, neither tetrodot oxin nor 5-(N,N-dimethyl)amiloride affected the mechanical function and ene rgy metabolism. These results suggested that inhibition of the Na+ channel or Na+/H+ exchan ger was effective in attenuating the H2O2-induced mechanical dysfunction an d metabolic derangements in the isolated perfused rat heart.