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

Br J Pharmacol. 1996 Apr;117(8):1744-8. doi: 10.1111/j.1476-5381.1996.tb15348.x.

Abstract

1. 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 micrograms 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. 2. Although, rilmenidine has a weak affinity for alpha(2)-adrenoceptors, pretreatment with idazoxan (10 micrograms kg-1, intracisternally i.c.), an imidazoline receptor antagonist which has also alpha(2)-adrenoceptor blocking potency, blocked the antiarrhythmic effect of rilmenidine (10 micrograms kg-1, i.v.). In contrast, pretreatment with rauwolscine (20 micrograms kg-1, i.c.), a classical alpha(2)-adrenoceptor antagonist with little affinity for imidazoline receptors, did not affect the effect of rilmenidine (10 micrograms kg-1, i.v.). Furthermore, bilateral vagotomy completely blocked the antiarrhythmic action of rilmenidine (10 micrograms kg-1, i.v.). 3. 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.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology
  • Analysis of Variance
  • Anesthetics, Inhalation
  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control*
  • Blood Pressure / drug effects
  • Dogs
  • Epinephrine / blood
  • Female
  • Halothane
  • Heart Rate / drug effects
  • Idazoxan / pharmacology
  • Imidazoline Receptors
  • Male
  • Oxazoles / pharmacology*
  • Receptors, Drug / drug effects
  • Receptors, Drug / physiology
  • Rilmenidine
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Anesthetics, Inhalation
  • Imidazoline Receptors
  • Oxazoles
  • Receptors, Drug
  • Yohimbine
  • Rilmenidine
  • Halothane
  • Idazoxan
  • Epinephrine