K-ATP CHANNELS CONTRIBUTE TO THE CARDIOPROTECTION OF PRECONDITIONING INDEPENDENT OF ANESTHETICS IN RABBIT HEARTS

The contribution of ATP sensitive potassium (K-ATP) channels to the in farct-size limiting effect of preconditioning is considered to be anae sthetic-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 preserva tion of these enzyme activities, induced by ischaemic preconditioning, as well as that induced by activation of A(1)-adenosine receptors, wa s examined in rabbits anaesthetized with either pentobarbital or ketam ine-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 pretreate d with the A(1)-adenosine receptor agonist R(-)-N-6-(2-phenylisopropyl ) adenosine. The protective effects of both ischaemic preconditioning and A(1)-adenosine receptor activation were prevented by 6 mg/kg, but not 3 mg/kg, of the K-ATP channel blocker, glibenclamide, in rabbits a naesthetized with pentobarbital, while these effects were prevented by 3 mg/kg of the blocker in rabbits anaesthetized with ketamine-xylazin e. Moreover, K-ATP channel opener, cromakalim, prevented the ischaemia -induced decreases in enzymatic activities in rabbits subjected to eit her type of anaesthesia. Thus, although the antagonistic effect of gli benclamide is blunted under pentobarbital, compared to ketamine-xylazi ne anaesthesia, K-ATP channels contribute to preservative actions inde pendent of the type of anaesthesia in the rabbit heart. (C) 1997 Acade mic Press Limited.