Cocaine sensitization of coronary artery contractions: mechanism of drug-induced spasm.

Illicit cocaine use has been associated with a high incidence of cardiovascular complications including coronary spasm, arrhythmias, myocardial infarction and sudden death. Adverse effects of cocaine have been attributed routinely to the consequences of increased concentrations of the adrenergic transmitter at its sites of action including the coronary vasculature. The present study examined non-neurogenic postsynaptic sites of cocaine action in cattle coronary arteries that could account for its clinical profile. It was found that cocaine (3.3 x 10(-5) M) greatly increased responses to potassium chloride (by 98.4 +/- 13.8%) that are totally dependent on extracellular calcium. However, contractions to a thromboxane A2 analog, which are much less dependent on extracellular calcium influx, were not increased significantly by cocaine. Cocaine (3.3 x 10(-5) M) more than doubled the magnitude of non-neurogenic responses to field stimulation, but these responses were not enhanced in the presence of a calcium channel antagonist. Spontaneously generated tone was magnified significantly by cocaine (3.3 x 10(-5) M) (by 127.5 +/- 45.2%), and this enhancement also was selectively antagonized by nifedipine. Subthreshold concentrations of the calcium channel opener, Bay K 8644, also were increased greatly by cocaine, and this magnification was antagonized by nifedipine. Cocaine did not magnify responses to norepinephrine that are inhibitory in cattle coronary arteries, and desmethylimipramine, a potent inhibitor of catecholamine uptake, had no sensitizing effects on responses to potassium chloride, norepinephrine or field stimulation. It is concluded that cocaine has a potent action on the calcium L channels, magnifying the effects of stimuli that make use of these channels in contractions.(ABSTRACT TRUNCATED AT 250 WORDS)