Interactions of Phenylephrine and Theophylline in Contractility and Excitability of Isolated Rabbit Left Atria

Rabbit left atria were driven electrically at frequencies from 6 to 240/min or higher. The contractile tension-frequency curve was significantly moved upward by phenylephrine (10-6 and 10-5 M). The positive inotropic effect was not influenced by propranolol but was markedly attenuated by phentolamine. Theophylline in a concentration (10-4 M) sufficient to potentiate the effect of isoproterenol did not alter the positive inotropic effect of phenylephrine. Cardiac excitability studied in preparations driven at high frequencies was reduced by phenylephrine, the effect being inhibited by phentolamine and potentiated by propranolol. The excitability was enhanced by isoproterenol. Theophylline potentiated the effect of isoproterenol but inhibited the effect of phenylephrine in a high concentration (10-5 M). It may be concluded that an enhancement of the contractile force by stimulation of myocardial alpha-receptors is not due to increased formation of cyclic AMP. Theophylline does not appear to change the effect of alpha-receptor stimulation on cardiac excitability but rather to unmask the effect of beta-receptor stimulation when high concentrations of phenylephrine are applied.