Differential influences of several alpha-adrenoceptor antagonists on alpha-adrenoceptor-mediated inotropic responses in the left atria of guinea-pigs.

Influences of several alpha-adrenoceptor antagonists on the triphasic time response curves of phenylephrine, which are characterized by an initial increasing phase followed by a declining phase and then a second increasing phase, were investigated in the guinea pig left atria pretreated with sotalol (5 x 10(-5) M) and driven at 0.2 Hz. Phenoxybenzamine (10(-6) M) blocked both the positive and the negative inotropic effects and resulted in disappearance of the characteristic pattern, although lower concentrations (10(-8)--10(-7) M) preferentially attenuated the positive phase. Phentolamine (10(-7)--6 x 10(-6) M) and yohimbine (10(-6)--10(-5) M) preferentially inhibited the negative phase and potentiated the positive inotropic effect, thus changing the pattern to a biphasic or a monophasic one. Prazosin depressed concentration-dependently the positive inotropic effect and blunted the triphasic pattern (10(-9)--10(-8) M) or altered the pattern to a biphasic one (10(-7) M). In the presence of 10(-6) M prazosin, only the negative inotropic effect was observed to subsist. This negative inotropic effect was antagonized by 3 x 10(-6) M phentolamine. The present results suggest that there may exist two distinct types of postsynaptic alpha-adrenoceptors in the left atria of guinea pigs, one type mediating the positive inotropic effect and the other type mediating the negative inotropic effect.