Protective action of clonidine against the arrhythmogenic and lethal effects of ouabain in guinea-pigs.
1. Clonidine (1.25, 2.5 and 5.0 micrograms kg-1) was studied for its effect on the cardiac arrhythmias and lethality induced by slow intravenous infusion of ouabain in guinea-pigs. 2. 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. 3. Idazoxan (100 micrograms kg-1, i.v.) abolished the antiarrhythmic effect of clonidine whereas corynanthine (1 mg kg-1, i.v.) had no such effect. 4. Clonidine inhibited the rate of the ouabain-induced rise in blood pressure and the peak pressor response. 5. In isolated paced left atria of the guinea-pig, clonidine (3.75 x 10(-4) M) did not offer any protection against rapid and/or irregular extrasystolic contractions induced by ouabain. 6. 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 alpha 2-adrenoceptors, without any direct antiarrhythmic effect on the myocardium.
Thomas
G P
GP
Department of Pharmacology, Christian Medical College, Vellore, India.
Stephen
P M
PM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male; D010042:Ouabain / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity
D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D010042:Ouabain; D001285:Atropine; D003000:Clonidine