DIFFERENTIATION BY CHOLINERGIC STIMULATION OF POSITIVE INOTROPIC ACTIONS MEDIATED VIA ALPHA-ADRENOCEPTORS AND BETA-ADRENOCEPTORS IN THE RABBIT HEART

In the isolated rabbit papillary muscle, experiments were carried out in order to elucidate whether or not cholinergic stimulation produces a differential antagonistic action on the positive inotropic effects mediated via β- and α-adrenoceptor stimulation. Carbachol (0.1-30 μM) alone scarcely affected the basal tension developed. The postive inotropic effects of phenylephrine (30 μM) in the presence of phentolamine and of isoprenaline, which were mediated via β-adrenoceptors, were markedly inhibited by carbachol. Carbachol (3 μM) shifted the dose-response curve for isoprenaline in a parallel manner, and that for phenylephrine with phentolamine to the right and downwards. Carbachol administered during induction of the positive inotropic effects via α-adrenoceptors by phenylephrine (30 μM) with pindolol or by methoxamine failed to inhibit these effects and increased further the tension developed. The dose-response curve for phenylephrine determined in the presence of pindolol was not affected by carbachol. The present results indicate that the cholinergic antagonism of the adrenergic action on the contractility of the mammalian ventricular myocardium is exerted specifically to the β-adrenoceptor-mediated action, but not to the α-adrenoceptor-mediated one. © 1979.