Release of noradrenaline proposed as a mechanisms for the positive inotropic action of dipyridamole.

In the arterially blood-perfused canine papillary muscle, i.a. injections of dipyridamole (10-300 mug) produced a dose-dependent increase in developed tension amounting to about 45% of the basal developed tension at 300 mug. The positive inotropic response to dipyridamole was greatly reduced by a prior i.a. injection of propranolol (10 mug) or by pretreatment with reserpine (0.2 mg/kg s.c. for 3 consecutive days) but not affected by a prior i.a. injection of tetrodotoxin (1 mug) or desmethylimipramine (3-10 mug). The positive inotropic response to dipyridamole reduced by pretreatment with reserpine was restored by i.a. infusion of noradrenaline (0.03 mug/min). Dipyridamole did not modify the positive inotropic responses to noradrenaline and tyramine. These results suggest that the positive inotropic response to dipyridamole is largely due to noradrenaline released from adrenergic nerve endings by a mechanism that differs from those operative in the action of tyramine or in liberation of noradrenaline upon excitation.