title: Influence of stimulation of myocardial alpha- as well as beta-adrenoceptors on the effect of digoxin in isolated electrically driven rabbit papillary muscles.
abstract: On isolated electrically driven rabbit papillary muscle the cardiac glycoside digoxin was infused at driving rates of 0.5, 1.0 and 2.0 Hz. Two effective concentrations of digoxin were determined: 1. that inducing the maximal inotropic effect (maximal inotropic concentration) and 2, that causing cardiac arrest (toxic concentration). The influence of the alpha-sympathomimetic drug phenylephrine and for comparison that of the beta-sympathomimetic drug isoprenaline on either concentration of digoxin was investigated. 1. Stimulation of alpha-adrenoceptors by phenylephrine at a rate of 0.5 Hz significantly decreased the maximal inotropic as well as the toxic concentration of digoxin by about 36%; this decrease was maximal under the influence of the EC25 of phenylephrine and could be blocked by phentolamine. Phenylephrine did not alter the maximal inotropic effect of digoxin. At a stimulus rate of 1.0 Hz the EC75 of phenylephrine still diminished significantly the effective concentrations of digoxin whereas under these conditions the EC25 was ineffective. At 2.0 Hz stimulation of myocardial alpha-adrenoceptors had no effect anymore on either the maximal inotropic or the toxic concentration of digoxin. 2. In contrast, stimulation of beta-adrenoceptors by isoprenaline at a driving rate of 2.0 Hz resulted in a pronounced decrease of maximal inotropic and toxic concentration of digoxin while the maximal positive inotropic effect exerted by digoxin was found to be not altered by isoprenaline. The decrease of the effective concentration of digoxin caused by isoprenaline was abolished by pindolol. At a driving rate of 1.0 Hz this effect was slightly attenuated but was completely absent at 0.5 Hz. 3. From these results it can be concluded that stimulation of either adrenoceptor, alpha- and beta-, increases the effectiveness of the cardiac glycoside digoxin, i.e. diminishes the maximal inotropic as well as its toxic concentration. While stimulation of alpha-adrenoceptors is effective only at low rates of stimulation that of beta-adrenoceptors is vice versa at higher ones, thus supporting the view of different mechanisms underlying stimulation of alpha- or beta-adrenoceptors.
mesh_terms: D000818:Animals; D004077:Digoxin / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D004077:Digoxin; D007545:Isoproterenol; D010646:Phentolamine