α-Adrenoceptors in the ventricular myocardium: clonidine, naphazoline and methoxamine as partial α-agonists exerting a competitive dualism in action to phenylephrine

Abstract

The α-sympathomimetic agonists, clonidine, naphazoline, methoxamine, oxymetazoline and phenylephrine were used to further characterize the α-adrenoceptors mediating the positive inotropic effect in the isolated papillary muscle of the rabbit heart. The maximal inotropic effects of these amines were compared with the effect of isoprenaline and it was examined whether or not these amines compete for α-adrenoceptors. On the papillary muscle stimulated at 0.5 Hz, phenylephrine showed a high affinity (pD 2 value = 6.13) and produced the most pronounced intrinsic activity of the α-sympathomimetic amines. Therefore, the intrinsic activity of phenylephrine, in the presence of prindolol (3 × 10 −8 M), was used for comparison with those of the other α-agonists. Clonidine caused a positive inotropic effect: the intrinsic activity amounted to 0.32 of that of phenylephrine; the affinity was the highest among the amines tested (pD 2 value = 6.46); its effect was inhibited by 10 −6 M phentolamine. The affinity and the intrinsic activity of naphazoline were slightly lower than those of clonidine. Methoxamine showed a relatively high intrinsic activity (0.56) but the lowest affinity (4.68). Oxymetazoline did not cause any positive inotropic effect. Clonidine, naphazoline and oxymetazoline antagonized the positive inotropic effect of phenylephrine, mediated via the α-adrenoceptors in the presence of 3 × 10 −8 M prindolol, in a competitive manner. This observation suggests that these α-sympathomimetic amines compete with phenylephrine for the same receptor site. Thus the present results provide additional evidence for α-adrenoceptors mediating the positive inotropic actions of sympathomimetic amines in the rabbit papillary muscle.