Evidence for Participation of Catecholamines in Cardiac Action of Ouabain: Positive Chronotropic Effect

Abstract

I 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-" M, and maximal response occurred at 4 x 10-M. The half-time of the ouabain effect was about 20 minutes. 3 The positive chronotropic effect of ouabain was reduced to 40% by f-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.