Kamibayashi T, Mammoto T, Hayashi Y, Yamatodani A, Takada K, Sasaki S, Yoshiya I
Department of Anesthesiology, Osaka University Faculty of Medicine, Japan.
Anesthesiology. 1995 Nov;83(5):1082-9. doi: 10.1097/00000542-199511000-00022.
alpha 2 Adrenoceptors in the central nervous system mediate various physiologic processes, including cardiovascular control. Recently, some of these actions have been reported to be mediated by a nonadrenergic receptor, namely an imidazoline receptor. The authors previously reported that dexmedetomidine, a selective alpha 2 agonist, prevents the genesis of halothane-epinephrine dysrhythmias through a central mechanism. Because dexmedetomidine also binds to imidazoline receptors, we performed the current study to examine the precise receptor mechanism involved in the antidysrhythmic property of dexmedetomidine.
Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. The dysrhythmogenic dose of epinephrine was defined as the smallest dose producing four or more premature ventricular contractions within 15-s period. We examined the antidysrhythmic action of dexmedetomidine in the presence of two kinds of alpha 2 antagonists, that is, agents that label imidazoline receptors and exert a pharmacologic action through imidazoline receptors (idazoxan and atipamezole) and agents that are nonimidazoline compounds and are lacking in pharmacologic action through imidazoline receptors (rauwolscine and L-659,066). They were given cerebroventricularly.
Idazoxan and atipamezole significantly inhibited the antidysrhythmic action of dexmedetomidine, whereas rauwolscine and L-659,066 did not.
Because alpha 2 antagonists having imidazoline or imidazole structures inhibited the antidysrhythmic action of dexmedetomidine, and the inhibition produced by the non-imidazoline alpha 2 antagonists was not significant, imidazoline receptors in the central nervous system are more responsible for the antidysrhythmic action of dexmedetomidine than are alpha 2 adrenoceptors.
中枢神经系统中的α2肾上腺素能受体介导多种生理过程，包括心血管控制。最近，据报道其中一些作用是由一种非肾上腺素能受体，即咪唑啉受体介导的。作者先前报道，选择性α2激动剂右美托咪定通过中枢机制预防氟烷 - 肾上腺素心律失常的发生。由于右美托咪定也与咪唑啉受体结合，我们进行了本研究以探讨右美托咪定抗心律失常特性所涉及的精确受体机制。
成年杂种犬用氟烷（1.3%）麻醉，并持续监测体动脉压和室性早搏。致心律失常剂量的肾上腺素定义为在15秒内产生四次或更多次室性早搏的最小剂量。我们在两种α2拮抗剂存在的情况下研究了右美托咪定的抗心律失常作用，这两种拮抗剂分别是标记咪唑啉受体并通过咪唑啉受体发挥药理作用的药物（伊达唑胺和阿替美唑）以及非咪唑啉化合物且不通过咪唑啉受体发挥药理作用的药物（育亨宾和L - 659,066）。它们通过脑室内给药。
伊达唑胺和阿替美唑显著抑制了右美托咪定的抗心律失常作用，而育亨宾和L - 659,066则没有。
由于具有咪唑啉或咪唑结构的α2拮抗剂抑制了右美托咪定的抗心律失常作用，而非咪唑啉α2拮抗剂产生的抑制作用不显著，因此中枢神经系统中的咪唑啉受体比α2肾上腺素能受体对右美托咪定的抗心律失常作用更具责任。
