Antiarrhythmic action of rilmenidine on adrenaline-induced arrhythmia via central imidazoline receptors in halothane-anaesthetized dogs.
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.
Mammoto
T
T
Department of Anesthesiology, Osaka University, Faculty of Medicine, Japan.
Kamibayashi
T
T
Hayashi
Y
Y
Yamatodani
A
A
Takada
K
K
Yoshiya
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005260:Female; D006221:Halothane; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D000077769:Rilmenidine; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018685:Anesthetics, Inhalation; D054755:Imidazoline Receptors; D010080:Oxazoles; D011955:Receptors, Drug; D015016:Yohimbine; D000077769:Rilmenidine; D006221:Halothane; D019329:Idazoxan; D004837:Epinephrine