Mechanism of the positive inotropic action of cocaine in the guinea pig atrium.

We studied the mechanism of the positive inotropic action of cocaine in isolated guinea pig atria superfused with Tyrode's solution at 31 degrees C while attached to a force transducer to measure peak tension developed, maximum velocity of development of tension, and time to peak tension. Cocaine 2.9 microM enhanced peak tension developed and velocity of development of tension, and prolonged time to peak tension. The increase in peak tension developed produced by cocaine was not affected by propranolol. On the other hand, the cocaine-induced increase in velocity of development of tension was reduced, but not abolished. In the presence of propranolol and phentolamine combined, the cocaine-induced prolongation of time to peak tension was abolished and the increases of both peak tension developed and velocity of development of tension were significantly smaller than those observed in the absence of the two adrenergic blockers. For all practical purposes, nifedipine completely abolished the increase in peak tension developed induced by cocaine. It is concluded that the positive inotropic effect of cocaine in the guinea pig atrial muscle is predominantly the result of adrenergic-dependent, both alpha- and beta- receptor mediated, as well as adrenergic-independent increases in calcium influx through the L-type calcium channels in the sarcolemma.