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Journal of Pharmacology And Experimental Therapeutics, Vol. 157, Issue 1, 149-158, 1967
Copyright © 1967 by American Society for Pharmacology and Experimental Therapeutics

EFFECT OF MORPHINE ON ELECTRICALLY-INDUCED RELEASE OF AUTONOMIC MEDIATORS IN THE RABBIT SINOATRIAL NODE

Barbara L. Kennedy 1 and Theodore C. West 1

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

The effect of morphine on the chronotropic response to various frequencies of cholinergic and adrenergic postganglionic intranodal nerve stimulation was studied in isolated rabbit sinoatrial node-right atrial preparations. The steady state beat interval was decreased in low concentrations, but it was increased in high concentrations of morphine. The negative chronotropic response produced by morphine was not inhibited by atropine, but it was readily reversed by washing. The negative chronotropic response following electrical stimulation of intrasinoatrial node cholinergic fibers was markedly reduced by morphine, whereas the positive chronotropic response to adrenergic nerve stimulation was not changed. Pretreatment of the preparation with hexamethonium or propranolol had no effect on the negative chronotropic response produced by cholinergic nerve stimulation, and pretreatment of the preparation with atropine or hexamethonium did not inhibit the adrenergic response produced by intranodal nerve stimulation. Hexamethonium, propranolol and atropine did not change the effect of morphine on the increase or on the decrease in beat interval produced by intranodal nerve stimulation. Morphine did not inhibit the chronotropic response produced by exogenously administered acetyicholine and norepinephrine. These studies indicate that morphine produces a relatively specific inhibition of the release of acetylcholine from cardiac postganglionic cholinergic fibers, whereas morphine has no effect on either the release of catecholamines from cardiac postganglionic adrenergic fibers or on the chronotropic response to the exogenous administration of neurohormones.

Submitted on December 12, 1966
Accepted on February 14, 1967




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Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics.