Differential blocking effects of atropine and gallamine on negative chronotropic and dromotropic responses to vagus stimulation in anesthetized dogs

Y Furukawa, DW Wallick and P Martin

Department of Investigative Medicine, Mt. Sinai Medical Center, Cleveland, Ohio.

The negative dromotropic response to cervical vagus stimulation was inhibited less than the negative chronotropic response to cervical vagus stimulation by the same dose of atropine in neurally decentralized, anesthetized dogs. Atropine and gallamine bind different muscarinic binding sites. We thus investigated the blocking effects of atropine and gallamine on the negative chronotropic and dromotropic responses to stimulation of the vagus nerves. We stimulated the intracardiac vagus nerves to the SA nodal area (sinoatrial fat pad stimulation) or to the atrioventricular nodal area (atrioventricular fat pad stimulation). Sinoatrial fat pad stimulation increased the sinus cycle length. Atrioventricular fat pad stimulation increased atrioventricular conduction time without affecting the cycle length. Atropine inhibited the chronotropic response to sinoatrial fat pad stimulation and the dromotropic response to atrioventricular fat pad stimulation in a dose-dependent manner. The ID50 for the chronotropic responses was less than that for the dromotropic responses. In contrast, gallamine inhibited the chronotropic and dromotropic responses in a similar dose-dependent manner. Physostigmine potentiated the chronotropic and dromotropic responses similarly but it did not change the blocking effects of atropine on the cardiac responses. These results suggest that the binding properties of the muscarinic receptors to the antagonists on the sinoatrial node are different from those on the atrioventricular node in the heart.

Volume 251, Issue 3, pp. 797-802, 12/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics