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Journal of Pharmacology And Experimental Therapeutics, Vol. 173, Issue 1, 145-151, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

CORRELATION OF CARDIAC SODIUM- AND POTASSIUM-ACTI-VATED ADENOSINE TRIPHOSPHATASE ACTIVITY WITH OUABAIN-INDTJCED INOTROPIC STIMULATION

TAI AKERA 1, FRAN S. LARSEN 1, and THEODORE M. BRODY 1

1 Department of Pharmacology, Michigan State University, East Lansing, Michigan

The effect of ouabain infusion on cardiac contractile force, electrocardiogram, blood pressure and adenosine triphosphatase (ATPase) activity [Mg++-dependent adenosine triphosphate (ATP) phosphohydrolase, Enzyme Commission no. 3.6. 1.3] was studied in open-chest, pentobarbital-anesthetized dogs with bilateral section of the cervical vagosympathetic nerves. A constant infusion of ouabain produced a progressive increase in cardiac contractile force and inhibition of atrioventricular conduction. Cardiac (Na+ + K+)-activated ATPase, but not Mg++-dependent ATPase, obtained from ouabain-infused animals had reduced specific activity. A significant correlation was observed between enhancement of cardiac contractile force and the inhibition of cardiac (Na+ + K+)-activated ATPase activity. Isoproterenol infusion or sympathetic stimulation produced an enhancement of cardiac contractile force but failed to alter cardiac (Na++ + K+)- activated ATPase activity. Addition of potassium during ouabain infusion prevented arrhythmias but failed to influence the inotropic stimulation and the reduction of cardiac (Na+ + K+)-activated ATPase activity. After the infusion of inotropic doses of ouabain, only (Na+ + K+)-activated ATPase obtained from cardiac tissue was inhibited. The enzymes isolated from kidney, brain and skeletal muscle had activities similar to controls. We conclude that the cardiac (Na+ + K+)-activated ATPase activity is inhibited specifically during inotropic stimulation by ouabain.

Submitted on October 20, 1969
Accepted on January 27, 1970




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