Attenuation by antioxidants of Na +/K + ATPase inhibition by toxic concentrations of isoproterenol in cultured rat myocardial cells

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We have reported previously that toxic concentrations of isoproterenol caused severe alterations in the structural integrity of the sarcolemma and mitochondria found in primary cultures of rat myocardial cells [8, 9]. Mitochondrial injury was observed 1.5 h after exposure to isoproterenol, whereas leakage of intracellular ions and enzymes was observed only after prolonged exposures (greater than 4 h). Ascorbic acid and sodium bisulfite prevented the cytotoxic effects of isoproterenol in our cell culture system. Takeo et al. [13] suggested that adrenochrome (an oxidative metabolite of epinephrine) specifically inhibits the activity of the sodium/potassium ATPase. Other investigators have shown that an indole metabolite of epinephrine inhibited actomyosin ATPase [1, 4]. These inhibitory actions may result from an interaction between the oxidative metabolites and sulfhydryl groups present in the enzyme [13]. Inhibition of the sodium/potassium ATPase is associated with an increase in the intracellular concentration of Na+ and Ca2+ and a decrease in intracellular K+. Changes in the intracellular concentration of these ions are commonly seen in heart cell damage and contractile failure [2]. The present study was designed to determine if isoproterenol, a synthetic catecholamine, inhibits the sodium/potassium ATPase activity in a primary culture system of rat myocardial cells.