Adrenergic-mediated effects of cocaine on the myocardial force-frequency relationship.

We studied the role of sarcolemmal alpha- and beta-adrenoceptors activation in the effects of cocaine on the positive force staircase in isolated guinea pig atria. The preparations were superfused with Tyrode's solution at 31 degrees C while attached to a force transducer to measure peak tension developed (PTD), maximum velocity of development of tension (Vmax T) and time to peak tension (TPT). The positive force staircase was not affected by propranolol or phentolamine, but it was abolished by nifedipine. Cocaine 1 mg/l (2.9 microM) enhanced PTD and Vmax T, while TPT remained unchanged. On the other hand, cocaine did not modify the increase in PTD induced by the increase in frequency of stimulation, but significantly reduced the magnitude of the increase in Vmax T. The cocaine-induced attenuation of the increase in Vmax T in response to changes in the frequency of stimulation was abolished by both propranolol and phentolamine. It is concluded that the effect of cocaine on the force-frequency relationship required background activation of alpha- and beta-adrenergic receptors.