FURTHER CHARACTERIZATION OF THE RECEPTOR MECHANISM INVOLVED IN THE ANTIDYSRHYTHMIC EFFECT OF DEXMEDETOMIDINE ON HALOTHANE EPINEPHRINE DYSRHYTHMIAS IN DOGS/

Background: alpha(2) Adrenoceptors in the central nervous system media te various physiologic processes, including cardiovascular control. Re cently, some of these actions have been reported to be mediated by a n onadrenergic receptor, namely an imidazoline receptor. The authors pre viously reported that dexmedetomidine, a selective alpha(2) agonist, p revents the genesis of halothane-epinephrine dysrhythmias through a ce ntral mechanism. Because dexmedetomidine also binds to imidazoline rec eptors, we performed the current study to examine the precise receptor mechanism involved in the antidysrhythmic property of dexmedetomidine . Methods: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and prematur e ventricular contractions. The dysrhythmogenic dose of epinephrine wa s defined as the smallest dose producing four or more premature ventri cular contractions within 15-s period. We examined the antidysrhythmic action of dexmedetomidine in the presence of two kinds of alpha(2) an tagonists, that is, agents that label imidazoline receptors and exert a pharmacologic action through imidazoline receptors (idazoxan and ati pamezole) and agents that are nonimidazoline compounds and are lacking in pharmacologic action through imidazoline receptors (rauwolscine an d L-659,066). They were given cerebroventricularly. Results: Idazoxan and atipamezole significantly inhibited the antidysrhythmic action of dexmedetomidine, whereas rauwolscine and L-659,066 did not. Conclusion s: Because alpha(2) antagonists having imidazoline or imidazole struct ures inhibited the antidysrhythmic action of dexmedetomidine, and the inhibition produced by the nonimidazoline alpha(2) antagonists was not significant, imidazoline receptors in the central nervous system are more responsible for the antidysrhythmic action of dexmedetomidine tha n are alpha(2) adrenoceptors.