title: Role of imidazoline-preferring receptors in the genesis of epinephrine-induced arrhythmias in halothane-anesthetized dogs.
abstract: BACKGROUND
  Drugs with a central alpha 2-adrenergic action can increase the threshold for halothane-epinephrine-induced arrhythmias. Recently, imidazoline-preferring receptors were shown to play a significant role in the hypotensive effect of alpha 2-adrenergic agonists containing an imidazole ring in their structure. To address the question of whether the antiarrhythmic property of the alpha 2-adrenergic agonists was caused by activation of alpha 2-adrenoceptors or imidazoline-preferring receptors in the central nervous system, the effect of an imidazoline (atipamezole) and a nonimidazoline (L-659,066 and yohimbine) alpha 2-adrenergic antagonist were examined as etiologic factors in the genesis of halothane-epinephrine-induced arrhythmias in dogs.
  
  
  METHODS
  Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and for premature ventricular contractions. The arrhythmogenic dose (AD) of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, was determined in the presence of atipamezole (an imidazoline compound that acrosses the blood-brain barrier), L-659,066 (a nonimidazoline compound that does not penetrate the blood-brain barrier), and yohimbine (a nonimidazoline compound that passes the blood-brain barrier). These drugs were administered either intravenously or into the cisterna magna to assess the site of action for changes in responsiveness.
  
  
  RESULTS
  Intravenous atipamezole decreased the AD of epinephrine in the dose-dependent fashion. However, neither L-659,066 nor yohimbine, administered peripherally, decreased the AD of epinephrine. Central administration of atipamezole also decreased the AD of epinephrine, while L-659,066, even if administered centrally, did not affect the AD of epinephrine in the presence of halothane.
  
  
  CONCLUSIONS
  Because the imidazoline ring-containing alpha 2-adrenergic antagonist (atipamezole) potentiated the halothane-epinephrine-induced arrhythmias and the nonimidazole alpha 2-adrenergic antagonist (L-659,066 and yohimbine) did not, it is possible that the imidazoline-preferring, rather than the alpha 2-adrenergic, receptor is responsible for the antiarrhythmic property of alpha 2-adrenergic agonists.
authors.affiliation: Department of Anesthesiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Kamibayashi
authors.forename: M
authors.initials: M
authors.lastname: Maze
authors.forename: A
authors.initials: A
authors.lastname: Yamatodani
authors.forename: K
authors.initials: K
authors.lastname: Sumikawa
authors.forename: M
authors.initials: M
authors.lastname: Kuro
authors.forename: I
authors.initials: I
authors.lastname: Yoshiya
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D005117:Cardiac Complexes, Premature / Q000139:chemically induced; D002946:Cisterna Magna; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006221:Halothane / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D011807:Quinolizines; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; C050701:atipamezole; D015016:Yohimbine; C055732:vatinoxan; D006221:Halothane; D004837:Epinephrine