INHIBITION OF CENTRALLY INDUCED VENTRICULAR ARRHYTHMIAS BY RILMENIDINE AND IDAZOXAN IN RABBITS

In a model of ventricular arrhythmias of central origin, we investigat ed the effects of rilmenidine, an oxazoline with antihypertensive prop erties, and idazoxan, an imidazoline that is an antagonist of the hypo tensive effects of rilmenidine. Bicuculline, a GABA(A) receptor antago nist, was administered intracisternally (i.c.) to produce arrhythmias in pentobarbitone anaesthetised rabbits; 10 mu g/kg bicuculline i.c. i nduced polymorphic ventricular ectopic beats and ventricular tachycard ia while blood pressure increased by about 50-60% and sinusal heart ra te decreased by about 20%. Rilmenidine, either administered intravenou sly (0.01, 0.1, 1 mg/kg i.v.) or i.c. (3, 10, 30 mu g/kg) dose-depende ntly prevented the occurrence of bicuculline-induced arrhythmias while , because of a lower base-line, the blood pressure values reached were less as compared to controls. Idazoxan administered i.v. (3, 10 mg/kg ) had a similar action. Idazoxan i.c. (15 mu g/kg) had no significant antiarrhythmic effect but antagonized in part the haemodynamic and ant iarrhythmic effects of rilmenidine (1 mg/kg i.v.; 30 mu g/kg i.c.). It is suggested that the antiarrhythmic effects observed with rilmenidin e are mainly mediated by blunting the bicuculline-induced increase in the sympathetic nervous output to the heart and the vascular beds. The se effects of rilmenidine are likely to originate both from the centra l and peripheral nervous system. The antiarrhythmic effects of idazoxa n i.v. might be related to a blocking action on alpha(2)-adrenoceptors at the level of the coronary arteries and other vascular beds.