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Journal of Pharmacology And Experimental Therapeutics, Vol. 153, Issue 1, 104-113, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics


THE INFLUENCE OF OUABAIN ON CHOLINERGIC RESPONSES IN THE SINOATRIAL NODE

Noboru Toda 1 and Theodore C. West 1

1 Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

The effect of ouabain on responsiveness to cholinergic influence was studied in the isolated vagus-atrial preparation of the rabbit. Atrial electrical and mechanical activity and transmembrane potentials from the sinoatrial (S-A) node were recorded. Stimulation of the isolated vagus nerve was used for cholinergic nerve stimulation. Acetylcholine was applied in graded concentrations to determine sensitivity to exogenous cholinergic influence. Ouabain at 5 x 10-8 and 2 x 10-7 g/ml increased contractile force without altering heart rate. Ouabain at 10-6 g/ml depressed contractile force, increased heart rate and induced arrhythmias. Augmentation of the response to vagal stimulation was observed in 2 x 10-7 g/ml of ouabain. At 10-6 g/ml, ouabain inhibited the negative chronotropic response to vagal stimulation. At the same concentration, the steady state maximal diastolic potential of S-A node cells was reduced, as was action potential amplitude, but hyperpolarization during vagal stimulation was increased. Sensitivity of the S-A node to exogenous acetylcholine was increased by 2 x 10-7 and 10-6 g/ml of ouabain, but the negative inotropic response to acetylcholine was reduced. Acetylcholine antagonized toxic actions of ouabain on pacemaker and atrial myocardium. Toxic effects of ouabain on S-A node fibers were shown to be comparable to the effects of rexuced external sodium concentration.

Accepted on January 25, 1966




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