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

• Published in: Journal of pharmacy and pharmacology 1999-09, Vol.51 (9), p.1049-1058
• Main Authors: HARA, A, ARAKAWA, J, XIAO, C.-Y, HASHIZUME, H, USHIKUBI, F, ABIKO, Y
• Format: Article
• Language: English
• Subjects: Amiloride - analogs & derivatives; Amiloride - pharmacology; Analysis of Variance; Animals; Biological and medical sciences; Cardiovascular system; Energy Metabolism - drug effects; Heart - drug effects; Hydrogen Peroxide - antagonists & inhibitors; Hydrogen Peroxide - toxicity; Lipid Peroxidation - drug effects; Male; Medical sciences; Miscellaneous; Myocardium - metabolism; Oxidants - antagonists & inhibitors; Oxidants - toxicity; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Tetrodotoxin - pharmacology
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357991773384

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 the mechanical and metabolic derangements induced by hydrogen peroxide (H2O2) was studied in the isolated perfused rat heart. The isolated rat heart was perfused aerobically at a constant flow rate and driven electrically. H2O2 (600 microM) decreased the left ventricular developed pressure and increased the left ventricular end-diastolic pressure (i.e. mechanical dysfunction), decreased the tissue levels of adenosine triphosphate and adenosine diphosphate (i.e. metabolic derangement), and increased the tissue level of malondialdehyde (i.e. lipid peroxidation). These mechanical and metabolic derangements induced by H2O2 were significantly attenuated by tetrodotoxin (3 microM) or 5-(N,N-dimethyl)-amiloride (15 microM). Neither tetrodotoxin nor 5-(N,N-dimethyl)-amiloride modified the tissue malondialdehyde level, which was increased by H2O2. In the normal (H2O2-untreated) heart, neither tetrodotoxin nor 5-(N,N-dimethyl)-amiloride affected the mechanical function and energy metabolism. These results suggested that inhibition of the Na+ channel or Na+/H+ exchanger was effective in attenuating the H2O2-induced mechanical dysfunction and metabolic derangements in the isolated perfused rat heart.