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Journal of Pharmacology And Experimental Therapeutics, Vol. 149, Issue 2, 225-232, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

MECHANISM FOR NICOTINE AND DMPP ON THE ISOLATED RAT ATRIA-VAGUS NERVE PREPARATION

Tzu Sung Chiang 1 and Floyd E. Leaders 1

1 Department of Pharmacology, University of Kansas Medical School, Kansas City, Kansas

The effects of nicotine and DMPP were studied in isolated rat atria preparations with vagus nerves intact. The influence of nicotine, DMPP, atropine, bretylium, hemicholinium (HC-3) with vagal stimulation, hexamethonium, and reserpine on the responses to administration of nicotine and DMPP also were studied.

Inhibition followed by stimulation of atrial rate and force of contraction was found when either nicotine or DMPP was added to the bath. The inhibitory phase of the response to nicotine was blocked by pretreatment with nicotine, atropine, bretylium or HC-3 with vagal stimulation. The stimulant phase was blocked by bretylium or HC-3 with vagal stimulation and was blocked and reversed to inhibition by hexamethonium.

The inhibitory phase of the response to DMPP also was blocked by pretreatment with nicotine, atropine, bretylium, HC-3 with vagal stimulation or hexamethonium. The stimulant phase, however, was not blocked by hexamethonium or HC-3 with vagal stimulation, but was greatly reduced by bretylium.

Bretylium alone produced a prominent positive inotropic effect, but the chronotropic response was negative. It did inhibit the response to vagal stimulation in this preparation, as did HC-3 when the vagus nerves were stimulated every 3 minutes. When the nerves were not stimulated previously, no inhibitory effect was observed, even when bretylium was present in the bath for 60 minutes.

Reserpine pretreatment greatly reduced the positive effects of DMPP and bretylium but not that of nicotine. Possible mechanisms concerning the action of nicotine and DMPP are discussed in the light of the effects of the pharmacologic blocking agents used.

Accepted on March 26, 1965




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Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics.