The positive inotropic action of serotonin (5-hydroxytryptamine) has extensively been demonstrated in the isolated perfused heart of cats, dogs and rabbits (1, 2), in the isolated auricle of the rabbit's heart (3, 4), in the cat papillary muscle (5), and in the heart of dog in situ (6). In reserpinized rabbits, however, serotonin does not produce a positive inotropic action (4). Accordingly, the serotonin induced increase in myocardial contractile force is presumably mediated by noradrenaline and adrenaline, which were liberated by the administration of serotonin . If this assumption is correct, beta-adrenergic blocking agents should be expected to block the positive inotropic action of serotonin.The present investigation was undertaken to examine this possibility , by comparing the presence or absence of a beta-adrenergic blocking drug on the positive inotropic action of serotonin.Normal dogs (8-11 kg) were anesthetized with pentobarbital sodium (3'3 mg/kg, i.v.). Under artificial respiration, the chest was opened and a strain-gage arch (7 , 8) was sutured to the right ventricular muscle for the measurement of the myocardial contractile force . Blood pressure was recorded by means of a pressure transducer from the right femoral artery . Propranolol (9) was chosen as the beta-adrenergic blocking agent in the present experiment , owing to the potent ability to block the beta-adrenergic receptors (10). A single dose of serotonin in the form of serotonin creatinine sulfate was injected at a rate of 50 pg/kg. A similar experiment was conducted in reserpinized dogs (9-12 kg). Reserpine (0.3 mg/kg) was given subcutaneously 24 hours prior to the experiment in 6 dogs, in an attempt to deplete the catecholamine stores (11). In I dog, a larger dose of reserpine (0.5 mg/kg) was given subcutaneously 48 hours and 24 hours before the experiment.Anesthetic doses of pentobarbital sodium for the reserpinized dogs were about 1/3 to 1/2 of those for normal dogs.As shown in the upper panel of Fig . 1, an intravenous injection of 50 pug/kg of serotonin into a normal dog, produced a transitory increase in the myocardial contractile force , and an increase in blood pressure corresponding to the positive inotropic response . A small fluctuation in blood pressure was observed immediately before a marked pressor response to serotonin . Propranolol (0.5 mg/kg), which was injected slowly into the vein, decreased the myocardial contractile force by about 50% ,