Evidence for participation of catecholamines in cardiac action of ouabain: positive chronotropic effect.
1 The shortening of cycle length (=positive chronotropic effect) by ouabain produced in isolated spontaneously beating atria of the guinea-pig was analyzed.2 The action of ouabain was dose-dependent; threshold response was seen at 1 x 10(-7) M, and maximal response occurred at 4 x 10(-7) M. The half-time of the ouabain effect was about 20 minutes.3 The positive chronotropic effect of ouabain was reduced to 40% by beta-adrenoceptor blockade (3.3 x 10(-9) M propranolol) or by reserpine-depletion of catecholamines. Incubation of reserpine-treated atria with noradrenaline partially restored the action of ouabain.4 The effect of ouabain was greatly dependent upon the calcium concentration. The optimal calcium level was 2.5 x 10(-3) M. Calcium and ouabain acted synergistically.5 Increasing calcium concentrations inhibited the positive chronotropic effect of noradrenaline in a manner similar to increasing ouabain concentrations.6 A hypothesis is proposed which explains the chronotropic effect of ouabain on the basis of two mechanisms: (1) increase of the catecholamine concentration affecting the pacemaker; (2) mobilization of calcium, i.e. increase of the biologically effective intracellular calcium level.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004562:Electrocardiography; D004566:Electrodes; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors
D002395:Catecholamines; D010042:Ouabain; D012110:Reserpine; D011433:Propranolol; D002118:Calcium; D009638:Norepinephrine