K(ATP) channels contribute to the cardioprotection of preconditioning independent of anaesthetics in rabbit hearts.
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.
Morita
Y
Y
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Sakyo-ku, Japan.
Murakami
T
T
Iwase
T
T
Nagai
K
K
Nawada
R
R
Kouchi
I
I
Akao
M
M
Sasayama
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D007545:Isoproterenol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014991:Xylazine / Q000494:pharmacology
D000777:Anesthetics; D002316:Cardiotonic Agents; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D014991:Xylazine; D007649:Ketamine; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D010424:Pentobarbital; D007545:Isoproterenol