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Journal of Pharmacology And Experimental Therapeutics, Vol. 141, Issue 3, 301-309, 1963
Copyright © 1963 by American Society for Pharmacology and Experimental Therapeutics

MODIFICATION BY RESERPINE OF THE RESPONSE OF THE ATRIAL PACEMAKER TO SYMPATHOMIMETIC AMINES

U. Trendelenburg 1, B. Gomez Alonso de la Sierra 1, and A. Muskus 1

1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The action of thirteen sympathomimetic amines on the rate of isolated guinea-pig atria was studied on normal preparations and on atria from reserpine-pretreated animals. The dose-response curves of the amines had a complex shape which was the result of two opposing components of action: an accelerating and a decelerating component. Pretreatment with reserpine revealed that some sympathomimetic amines have direct accelerating effects (norepinephrine, phenylephrine, synephrine), others have an indirect accelerating action (tyramine-like amines), while a third group has both direct and indirect accelerating effects (ephedrine, phenylpropanolamine). Whereas pretreatment with reserpine abolished the indirect accelerating action, it did not affect the decelerating action of sympathomimetic amines.

With most sympathomimetic amines the accelerating component is maximally effective at a concentration at which the decelerating component is also manifest; furthermore throughout the range of the descending limb of the doseresponse curve the accelerating component persists.

The effect of ephedrine on the response of atria to norepinephrine was studied; ephedrine was found to antagonize the action of norepinephrine at the beta-receptor of the pacemaker. In this respect, ephedrine resembled dichloroisoproterenol; however, it differed from the latter in causing supersensitivity to norepinephrine when tested in low concentrations.

Submitted on April 10, 1963
Accepted on June 3, 1963




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Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics.