Induction by endogenous noradrenaline of an alpha 1-adrenoceptor-mediated positive inotropic effect in rabbit papillary muscles.

1. The possible involvement of alpha 1-adrenoceptors in the inotropic and electrophysiological responses to endogenous noradrenaline released by tyramine was examined in rabbit papillary muscles. 2. A concentration-dependent positive inotropic effect was produced by tyramine. This effect of tyramine was not observed in muscles from rabbits pretreated with reserpine. 3. The positive inotropic effect of tyramine was greatly inhibited by propranolol, but not altered by prazosin. However, when beta-adrenoceptors were blocked by pretreatment with propranolol, tyramine still produced a positive inotropic effect, an effect which was antagonized by prazosin. 4. Tyramine caused a decrease in action potential duration (APD) and an increase in action potential amplitude in a concentration-dependent manner. Isoprenaline also produced the same electrophysiological effects. These electrophysiological effects of both agents were inhibited by propranolol. 5. When beta-adrenoceptors were blocked by propranolol, the observed prazosin-sensitive positive inotropic effect of tyramine was not accompanied by any change in APD. In contrast, APD was markedly prolonged by alpha 1-adrenoceptor stimulation with phenylephrine in the presence of propranolol, in association with the positive inotropic effect. 6. It is concluded that in rabbit papillary muscles, endogenous noradrenaline causes a positive inotropic effect predominantly mediated by beta-adrenoceptors, but can still evoke a positive inotropic effect through alpha 1-adrenoceptors when beta-adrenoceptor stimulation is eliminated. This suggests that the alpha 1-adrenoceptor-mediated positive intropic mechanism(s) may be masked by simultaneous activation of beta-adrenoceptors. In addition, this study indicates that APD prolongation is not involved in the alpha 1-adrenoceptor-mediated inotropic responses to endogenous noradrenaline.