Protective action of clonidine against the arrhythmogenic and lethal effects of ouabain in guinea‐pigs

Abstract

Clonidine (1.25, 2.5 and 5.0 μg kg−1) was studied for its effect on the cardiac arrhythmias and lethality induced by slow intravenous infusion of ouabain in guinea‐pigs. Clonidine produced significant delays in the onset of the arrhythmic stages and lethality. However, clonidine did not offer any such protection in reserpinised guinea‐pigs, whereas its effects were unaltered in atropinized guinea‐pigs. Idazoxan (100 μg kg−1, i.v.) abolished the antiarrhythmic effect of clonidine whereas corynanthine (1 mg kg−1, i.v.) had no such effect. Clonidine inhibited the rate of the ouabain‐induced rise in blood pressure and the peak pressor response. In isolated paced left atria of the guinea‐pig, clonidine (3.75 × 10−4 m) did not offer any protection against rapid and/or irregular extrasystolic contractions induced by ouabain. It is concluded that the antiarrhythmic effect of clonidine is due to its effects on the indirect neural components of digitalis toxicity mediated by the stimulation of α2‐adrenoceptors, without any direct antiarrhythmic effect on the myocardium. 1991 British Pharmacological Society