Interactions between the autonomic nervous system and the cardiovascular effects of ouabain in guinea-pigs

Anaesthetized guinea-pigs were intoxicated with an intravenous infusion of ouabain. This infusion induced a marked pressor response which was reduced in bilaterally adrenalectomized or pithed animals. Ouabain produced initial bradyarrhythmias in 60% of guinea-pigs. Bilateral vagotomy or pretreatment with atropine abolished the bradyarrhythmias and sensitized the animals to the arrhythmic effects of ouabain. Pithing or beta-adrenoceptor blockade reduced the potency of ouabain for producing arrhythmias, but bilateral adrenalectomy did not give protection. Preferential alpha 2-adrenoceptor stimulation with clonidine (10-300 micrograms . kg-1 i.v.) also reduced the arrhythmogenic effects of ouabain, whereas no protection was found with St 91, a clonidine related compound which does not cross the blood-brain barrier. The effect of clonidine was antagonized by piperoxan. Preferential alpha 2-adrenoceptor blockade with piperoxan (6 mg . kg-1 i.v.) did not change the pressor response to ouabain, but sensitized the animals to the arrhythmogenic effects of ouabain. In contrast, the preferential alpha 1-antagonistic agent AR-C 239 (0.3 mg . kg-1 i.v.) abolished the pressor response to ouabain and in addition increased the dose of ouabain required to produced ventricular premature beats and ventricular fibrillation. These experiments indicate: (i) that ouabain produces in guinea-pigs a pressor response which seems to be due to catecholamine release from the adrenal medulla probably by an action on the central nervous system; (ii) that the ventricular arrhythmias induced by ouabain are due in part to stimulation of the central nervous system leading to an increase in beta-adrenoceptor activity; (iii) that central alpha-adrenoceptors appear to be involved in the arrhythmogenic effects of ouabain, as clonidine reduced these effects. On the other hand piperoxan, a preferential alpha 2-adrenoceptor antagonist did not change the pressor response to ouabain and increased the arrhythmogenic effects whereas AR-C 239 had opposite effects.