Abstract

Nicotine exhibits marked positive inotropic activity at a concentration of 2 x 10^-5 g/ml, or greater on the noninnervated heart of the 4-day-old chick embryo. There usually is observed an initial transient positive chronotropic effect which is followed by a decrease in heart rate. Higher concentrations of nicotine produce more pronounced negative chronotropic effects. Innervation does not significantly alter the cardiostimulant responses to nicotine. Essentially similar positive inotropic and chronotropic effects are produced by tetramethylammonium iodide (10^-4 g/ml) and acetylcholine chloride (10^-4 g/ml) on the atropinized embryonic heart.

Dichioroisoproterenol, which blocks the effects of epinephrine on the heart of the 4-day-old chick embryo, abolishes the cardiostimulant responses to nicotine but not those to barium chloride or ouabain. A congener of choline 2:6-xylyl ether, trimethyl (2-(2,6-xylyloxy)propyll ammonium chloride, which interferes with release and/or synthesis of the adrenergic mediator, blocks the cardiac responses to nicotine but not to epinephrine. Reserpine markedly reduces the catecholamine concentration of the 15-day-old embryonic heart and significantly decreases the positive inotropic response to nicotine by the heart of the 5-day-old embryo. Significant amounts of catecholamines, as demonstrated by spectrophotofluorometric methods, are present in the 4-day-old embryonic chick heart.

It may be concluded from the data presented that the positive inotropic and chronotropic effects of nicotine and certain other ganglionic stimulants are not dependent on the presence of sympathetic nerve endings in the heart. The evidence further suggests that there exist between the postganglionic sympathetic nerve endings and the adrenergic receptors in the heart certain structures which contain epinephrine-like material(s). Nicotine and similar agents cause a release of this material which in turn effects the positive inotropic and chronotropic responses.