DIFFERENTIAL INFLUENCES OF SEVERAL α-ADRENOCEPTOR ANTAGONISTS ON α-ADRENOCEPTOR-MEDIATED INOTROPIC RESPONSES IN THE LEFT ATRIA OF GUINEA PIGS

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Influences of several α-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 (5×10-5 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 (10-7-6×10-6 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 3×10-6 M phentolamine. The present results suggest that there may exist two distinct types of postsynaptic α-adrenoceptors in the left atria of guinea pigs, one type mediating the positive inotropic effect and the other type mediating the negative inotropic effect.
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