Cardiac glycosides: relationship among active 86Rb uptake, (Na+,K+)-ATPase activity, and inotropy in guinea pig heart.
Relationships among positive inotropic responses, (Na+,K+)-ATPase inhibition, and sodium pump activities were studied using paced Langendorff preparations of guinea pig heart. (Na+,K+)-ATPase activity was estimated from the initial velocity of [3H] ouabain binding in ventricular homogenates, and sodium pump activity from ouabain-sensitive 86Rb uptake of ventricular slices. These parameters were measured in control, or in ouabain-or digitoxin-treated hearts either at the time of inotropic response or during the course of drug washout and compared with inotropy in the same heart. Perfusion of ouabain or digitoxin caused an increase in contractile force and a decrease in the initial velocity of ATP-dependent [3H] ouabain binding. The levels of [3H] ouabain binding in homogenates observed after a long incubation period were not different in ouabain-perfused and control homogenates, indicating that the nonlabeled ouabain bound to (Na+,K+)-ATPase during Langendorff perfusion was exchangeable with [3H] ouabain. Perfusion of drug-free solution after a 20-min perfusion of the isolated heart with either ouabain or digitoxin resulted in a loss of inotropic response and a recovery of the inhibition of the initial velocity of ATP-dependent [3H] ouabain binding. Inotropic responses to digitoxin during perfusion and subsequent loss during washout were accompanied by a reduction and subsequent recovery of ouabain-sensitive 86Rb uptake. Thus, it would appear that with cardiac glycosides, a relationship exists among cardiac contractile force, the inhibition of cardiac (Na+,K+)-ATPase, and the inhibition of the sodium pump activity. The inhibition of (Na+,K+)-ATPase and sodium pump because of cardiac glycoside perfusion of the isolated beating heart was reversible.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D004074:Digitoxin / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology
D010042:Ouabain; D012964:Sodium; D004074:Digitoxin; D000251:Adenosine Triphosphatases; D012413:Rubidium; D011188:Potassium