Morita Y, Murakami T, Iwase T, Nagai K, Nawada R, Kouchi I, Akao M, Sasayama S
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Sakyo-ku, Japan.
J Mol Cell Cardiol. 1997 Apr;29(4):1267-76. doi: 10.1006/jmcc.1996.0364.
The contribution of ATP sensitive potassium (K(ATP)) channels to the infarct-size limiting effect of preconditioning is considered to be anaesthetic-dependent in the rabbit heart. It has previously been reported that ischaemic preconditioning prevents ischaemia-induced reductions in activities of sarcolemmal adenylate cyclase (AC) and Na+, K(+)-ATPase. Anaesthetic dependency of the role of K(ATP) channels in the preservation of these enzyme activities, induced by ischaemic preconditioning, as well as that induced by activation of A1-adenosine receptors, was examined in rabbits anaesthetized with either pentobarbital or ketamine-xylazine and subjected to 20 min of regional ischaemia. Adenylate cyclase and Na+, K(+)-ATPase activities were lower in the ischaemic than in the non-ischaemic region of the hearts in control rabbits, but not in animals subjected to ischaemic preconditioning, or those pretreated with the A1-adenosine receptor agonist R(-)-N6-(2-phenylisopropyl) adenosine. The protective effects of both ischaemic preconditioning and A1-adenosine receptor activation were prevented by 6 mg/kg, but not 3 mg/kg, of the K(ATP) channel blocker, glibenclamide, in rabbits anaesthetized with pentobarbital, while these effects were prevented by 3 mg/kg of the blocker in rabbits anaesthetized with ketamine-xylazine. Moreover, K(ATP) channel opener, cromakalim, prevented the ischaemia-induced decreases in enzymatic activities in rabbits subjected to either type of anaesthesia. Thus, although the antagonistic effect of glibenclamide is blunted under pentobarbital, compared to ketamine-xylazine anaesthesia, K(ATP) channels contribute to preservative actions independent of the type of anaesthesia in the rabbit heart.
在兔心脏中，三磷酸腺苷敏感性钾（K(ATP)）通道对预处理梗死面积限制作用的贡献被认为是依赖麻醉的。此前有报道称，缺血预处理可防止缺血诱导的肌膜腺苷酸环化酶（AC）和Na +，K(+)-三磷酸腺苷酶活性降低。在用戊巴比妥或氯胺酮-赛拉嗪麻醉并经历20分钟局部缺血的兔中，研究了K(ATP)通道在缺血预处理以及A1-腺苷受体激活诱导的这些酶活性保存中的作用的麻醉依赖性。对照组兔心脏缺血区域的腺苷酸环化酶和Na +，K(+)-三磷酸腺苷酶活性低于非缺血区域，但在经历缺血预处理的动物或用A1-腺苷受体激动剂R(-)-N6-(2-苯异丙基)腺苷预处理的动物中并非如此。在用戊巴比妥麻醉的兔中，6mg/kg而非3mg/kg的K(ATP)通道阻滞剂格列本脲可阻止缺血预处理和A1-腺苷受体激活的保护作用，而在用氯胺酮-赛拉嗪麻醉的兔中，3mg/kg的阻滞剂可阻止这些作用。此外，K(ATP)通道开放剂克罗卡林可防止两种麻醉类型的兔缺血诱导的酶活性降低。因此，尽管与氯胺酮-赛拉嗪麻醉相比，戊巴比妥下格列本脲的拮抗作用减弱，但K(ATP)通道在兔心脏中对保护作用的贡献与麻醉类型无关。
