EVIDENCE FOR PARTICIPATION OF CATECHOLAMINES IN CARDIAC ACTION OF OUABAIN: POSITIVE CHRONOTROPIC EFFECT

Abstract

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 × 10⁻⁷ m, and maximal response occurred at 4 × 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 β-adrenoceptor blockade (3.3 × 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 × 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.