Induction by endogenous noradrenaline of an α1‐adrenoceptor‐mediated positive inotropic effect in rabbit papillary muscles

Article date: August 1993

By: Yuichi Hattori, Youji Takeda, Haruaki Nakaya, Morio Kanno, in Volume 109, Issue 4, pages 1232-1238

The possible involvement of α1‐adrenoceptors in the inotropic and electrophysiological responses to endogenous noradrenaline released by tyramine was examined in rabbit papillary muscles.

A concentration‐dependent positive inotropic effect was produced by tyramine. This effect of tyramine was not observed in muscles from rabbits pretreated with reserpine.

The positive inotropic effect of tyramine was greatly inhibited by propranolol, but not altered by prazosin. However, when β‐adrenoceptors were blocked by pretreatment with propranolol, tyramine still produced a positive inotropic effect, an effect which was antagonized by prazosin.

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.

When β‐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 α1‐adrenoceptor stimulation with phenylephrine in the presence of propranolol, in association wh the positive inotropic effect.

It is concluded that in rabbit papillary muscles, endogenous noradrenaline causes a positive inotropic effect predominantly mediated by β‐adrenoceptors, but can still evoke a positive inotropic effect through α1‐adrenoceptors when β‐adrenoceptor stimulation is eliminated. This suggests that the α1‐adrenoceptor‐mediated positive intropic mechanism(s) may be masked by simultaneous activation of β‐adrenoceptors. In addition, this study indicates that APD prolongation is not involved in the α1‐adrenoceptor‐mediated inotropic responses to endogenous noradrenaline.

The possible involvement of α1‐adrenoceptors in the inotropic and electrophysiological responses to endogenous noradrenaline released by tyramine was examined in rabbit papillary muscles.

A concentration‐dependent positive inotropic effect was produced by tyramine. This effect of tyramine was not observed in muscles from rabbits pretreated with reserpine.

The positive inotropic effect of tyramine was greatly inhibited by propranolol, but not altered by prazosin. However, when β‐adrenoceptors were blocked by pretreatment with propranolol, tyramine still produced a positive inotropic effect, an effect which was antagonized by prazosin.

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.

When β‐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 α1‐adrenoceptor stimulation with phenylephrine in the presence of propranolol, in association wh the positive inotropic effect.

It is concluded that in rabbit papillary muscles, endogenous noradrenaline causes a positive inotropic effect predominantly mediated by β‐adrenoceptors, but can still evoke a positive inotropic effect through α1‐adrenoceptors when β‐adrenoceptor stimulation is eliminated. This suggests that the α1‐adrenoceptor‐mediated positive intropic mechanism(s) may be masked by simultaneous activation of β‐adrenoceptors. In addition, this study indicates that APD prolongation is not involved in the α1‐adrenoceptor‐mediated inotropic responses to endogenous noradrenaline.

DOI: 10.1111/j.1476-5381.1993.tb13754.x

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