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EVIDENCE FOR PARTICIPATION OF CATECHOLAMINES IN CARDIAC ACTION OF OUABAIN: POSITIVE CHRONOTROPIC EFFECT
Author(s) -
SEIFEN E.
Publication year - 1974
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1974.tb09665.x
Subject(s) - chronotropic , ouabain , reserpine , calcium , medicine , endocrinology , propranolol , chemistry , biology , sodium , heart rate , blood pressure , organic chemistry
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.