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Published on: September 16, 2015
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 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.
Insights
Ouabain accelerates heart rate in guinea-pig atria by influencing catecholamines and intracellular calcium levels. This positive chronotropic effect is dose-dependent and modulated by beta-adrenoceptor blockade and calcium concentration.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cellular Biology
Background:
- Ouabain is a cardiac glycoside known to affect heart contractility.
- The precise mechanisms underlying ouabain's chronotropic effects require further elucidation.
Purpose of the Study:
- To analyze the positive chronotropic effect of ouabain in isolated guinea-pig atria.
- To investigate the roles of catecholamines and calcium in mediating ouabain's action.
Main Methods:
- Isolated spontaneously beating guinea-pig atria were used.
- Experiments involved varying ouabain concentrations, beta-adrenoceptor blockade (propranolol), catecholamine depletion (reserpine), and calcium concentrations.
Main Results:
- Ouabain exhibited a dose-dependent positive chronotropic effect with a half-time of approximately 20 minutes.
- The effect was attenuated by beta-adrenoceptor blockade and catecholamine depletion, but partially restored by noradrenaline.
- Ouabain's action was highly dependent on calcium concentration, with synergistic effects observed.
Conclusions:
- Ouabain exerts its positive chronotropic effect through at least two mechanisms: enhancing pacemaker catecholamine concentration and increasing intracellular calcium levels.
- Calcium concentration plays a critical role in modulating both ouabain and noradrenaline effects on heart rate.
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