Triphasic time course of inotropic effect mediated by .ALPHA.-adrenoceptors in the left atria of guinea pigs.

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Abstract
The time course of the inotropic effects of phenylephrine in the presence of sotalol was investigated in the electrically driven left atria of quinea pigs. Phenylephrine at a concentration of 10-5 M in the presence of sotalol (5 .times. 10-5 M) produced triphasic time response curves which consisted of an initial positive inotropic phase followed by a negative inotropic phase and then a 2nd positive inotropic phase, at a rate of 0.2 Hz, whereas isoproterenol (10-8 M) induced a monophasic time course of the positive inotropic effect. Phenoxybenzamine (10-6 M) or phentolamine (6 .times. 10-6 M) depressed the inotropic effects induced by phenylephrine in the presence of sotalol and abolished the triphasic pattern of the time response curves. The negative inotropic effect leading to the occurrence of the triphasic time course was concentration and frequency dependent, i.e., it became more manifest with increase in the concentration of phenylephrine and with decrease in the stimulation frequency. At an extremely low frequency (1 beat/min), phenylephrine produced an insignificant increase in the contractile force and the characteristic triphasic pattern did not appear. Stimulation of .alpha.-adrenoceptors produces a frequency-dependent negative and positive inotropic effect in the left atria of guinea pigs.