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.