Antiarrhythmic action of rilmenidine on adrenaline‐induced arrhythmia via central imidazoline receptors in halothane‐anaesthetized dogs

Abstract

To elucidate the role of central imidazoline receptors in the genesis of adrenaline‐induced arrhythmias under halothane anaesthesia, we investigated the effects of rilmenidine, a selective agonist at imidazoline receptors, on this type of arrhythmia in dogs. Rilmenidine (1, 3, 10 μg kg−1, i.v.) did not affect basal haemodynamic parameters (heart rate and blood pressure), but dose‐dependently inhibited adrenaline‐induced arrhythmias under halothane anaesthesia. Although, rilmenidine has a weak affinity for α2‐adrenoceptors, pretreatment with idazoxan (10 μg kg−1, intracistenally i.c.), an imidazoline receptor antagonist which has also α2‐adrenoceptor blocking potency, blocked the antiarrhythmic effect of rilmenidine (10 μg kg−1, i.v.). In contrast, pretreatment with rauwolscine (20 μg kg−1, i.c.), a classical α2‐adrenoceptor antagonist with little affinity for imidazoline receptors, did not affect the effect of rilmenidine (10 μg kg−1, i.v.). Furthermore, bilateral vagotomy completely blocked the antiarrhythmic action of rilmenidine (10 μg kg−1, i.v.). It is suggested that the antiarrhythmic action of rilmenidine is due to the activation of central imidazoline receptors and that vagal tone is critical for this action of rilmenidine.

Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits

“…In fact, rilmenidine was able to blunt centrally induced ventricular arrhythmias through the inhibition of sympathetic hyperactivity in an experimental model of pharmacological activation of the central nervous system with bicuculline in anesthetized rabbits (21). Moreover, rilmenidine dose-dependently inhibits adrenaline-induced arrhythmias under halothane anesthesia in dogs, acting on central imidazoline receptors (22). These investigators suggested that the antiarrhythmic properties of rilmenidine in this particular experimental model result, at least in part, from simultaneous increases in vagal tone and baroreceptor sensitivity (22).…”

“…Moreover, rilmenidine dose-dependently inhibits adrenaline-induced arrhythmias under halothane anesthesia in dogs, acting on central imidazoline receptors (22). These investigators suggested that the antiarrhythmic properties of rilmenidine in this particular experimental model result, at least in part, from simultaneous increases in vagal tone and baroreceptor sensitivity (22). Using an identical experimental model, Hayashi et al (23) demonstrated that the arrhythmogenic dose of adrenaline decreases in a dose-dependent manner only after treatment with a 2 -adrenoceptor antagonists with an imidazoline structure but not with non-imidazoline antagonists such as yohimbine.…”

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

“…Rilmenidine dose dependently inhibits adrenaline-induced dysrhythmias under halothane anaesthesia in dogs [41]. This action was blocked by bilateral vagotomy and by pretreatment with a nonspecific alpha-2 adrenoceptor and imidazoline receptor antagonist idazoxan intracisternally.…”

Perioperative Use of Dexmedetomidine Is Associated With Decreased Incidence of Ventricular and Supraventricular Tachyarrhythmias After Congenital Cardiac Operations

“…Beyond its well known properties, a recent study has shown that dexmedetomidine has potential antiarrhythmic properties and can be used for the acute treatment of pediatric supraventricular tachyarrhythmias including junctional ectopic, atrial ectopic and reentrant type tachycardias [7]. In addition, animal studies have demonstrated that activation of imidazoline and alpha-2 adrenoceptors in the central nervous system, prevents adrenaline-induced ventricular tachycardia and that stimulation of the vagus nerve may be critical for this antiarrhythmic effect [8–11]. …”