Summary
In order to determine whether a prolonged inhibition of cardiac Na+, K+-ATPase causes a compensatory or adaptive change in this enzyme, the relationships among serum digoxin concentration, binding of digoxin to the enzyme and cardiac Na+, K+-ATPase and sodium pump activity were studied in dogs chronically treated with digoxin. Digoxin was injected intravenously twice daily up to 4 weeks. Two hours after the injection of a single non-toxic dose of digoxin, Na+, K+-ATPase and sodium pump activities were inhibited quantitatively in a manner corresponding to the binding of digoxin to the enzyme. The magnitude of sodium pump inhibition was reduced 12 h after the digoxin injection, with simultaneous decreases in serum digoxin concentration and the binding of digoxin to the enzyme. After 1 or 4 weeks of digoxin treatment with non-toxic doses, the relationships among serum digoxin concentration, binding of digoxin to cardiac Na+, K+-ATPase and the degree of cardiac Na+, K+-ATPase or sodium pump inhibition remained unchanged. The magnitude of the inhibition was related to serum digoxin concentrations and digoxin binding to cardiac Na+, K+-ATPase, in a manner similar to that observed after a single digoxin injection. After 4 weeks of digoxin treatment with toxic doses, these relationships were also unaffected. It was concluded that prolonged digoxin treatment fails to alter the inhibition of myocardial Na+, K+-ATPase by this agent.
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This work was supported by U.S. Public Health Service Grant HL-16052.
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Ku, D.D., Akera, T., Brody, T.M. et al. Chronic digoxin treatment on canine myocardial Na+, K+-ATPase. Naunyn-Schmiedeberg's Arch. Pharmacol. 301, 39–47 (1977). https://doi.org/10.1007/BF00501262
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DOI: https://doi.org/10.1007/BF00501262