THE NEGATIVE INOTROPIC ACTION OF EPHEDRINE AND ITS MODIFICATION BY VARIOUS AGENTS

¹ Department of Pharmacology, College of Medical Sciences, University of Minnesota, Minneapolis, Minnesota

The isolated cat papillary muscle was employed to study the negative inotropic action of ephedrine. Exposure of this muscle to increasing concentrations of the sympathomimetic amine revealed that it produced a maximal positive inotropic effect at a concentration of 1 x 10^-5 M. At higher concentrations there was enhanced contractility but the magnitude of the response was less. At concentrations greater than 1 x 10^-3 M, ephedrine produced negative inotropic responses. Atropine (2.8 x 10^-5 M) enhanced the positive inotropic responses to low concentrations of ephedrine. The negative inotropic response produced by ephedrine at 1 x 10^-3 M was converted to a positive inotropic response when the muscle was pretreated with a high concentration of atropine (1.7 x 10^-4 M). Physostigmine reduced the positive inotropic response produced by an ephedrine concentration of 1 x 10^-5 M. In the presence of dichloroisoproterenol, concentrations of ephedrine, which in the absence of this beta adrenergic blocking agent produced only positive inotropic responses, elicited only negative inotropic responses. The bathing media from papillary muscles exposed to a concentration of ephedrine that elicited a negative inotropic response caused a contraction of the rectus abdominis muscle of the frog in 5 of 10 experiments. When contraction of the rectus abdominis muscle did occur upon exposure to such bathing fluid, the effect was prevented by prior treatment of the muscle with d-tubocurarine. This same concentration of ephedrine in a medium not exposed to a papillary muscle did not cause contraction of the rectus abdominis muscle. These findings, for the most part, can be explained if it is assumed that ephedrine releases acetylcholine or an acetylcholine-like material from the papillary muscle.