Papaverine-induced changes on cardiac inotropism with special reference to a D-propranolol antagonism

Contractile responses were analyzed in the rat paced left atrium. Positive inotropic effects were papaverine dose-dependent with an increase in rate of tension development (dT/dt) and time to peak tension, with prolongation in the total duration of contraction. Reserpinized preparations did not modify papaverine response but several treatments inhibited it, i.e., either doubling or halving [Ca2+]0, as well as the addition of D-propranolol. Incubation of tissues with papaverine (1 hr) changed the usual dose-response curve to isoproterenol into a low, monotonous effect, independent of the agonist dose. Neither high nor low [Ca2+]0 could correct this action. D-propranolol restored the isoproterenol response but significantly blocked it. Under the same conditions, phenylephrine showed similar qualitative effects as above, though no significant differences were found in control vs. the various procedures tested. These results strongly suggest that papaverine provokes an initial calcium release followed by a sustained inhibition. In addition its site of action is the same as that of D-propranolol.