The role of ATP-sensitive potassium channels in the mechanism of ischemic preconditioning.
We clarified the role of K(ATP) channels in the mechanism of ischemic preconditioning by using K(ATP) channel opener, nicorandil, and K(ATP) channel inhibitor, glibenclamide. Forty anesthetized dogs were divided into five groups: (a) control (C), (b) ischemic preconditioning (PC), (c) intravenous infusion of nicorandil before PC (Ni), (d) glibenclamide pretreated with PC (Gl + PC), and (e) glibenclamide pretreated with Ni (Gl + Ni). All groups were followed by 60-min ischemia and 60-min reperfusion and analyzed by the biochemical procedures. At the end of 60-min reperfusion, percentage of segment shortening in C indicated paradoxic bulging. This value was significantly recovered in PC and Ni, but it was still negative in Gl + PC and Gl + Ni. Ca2+ -adenosine triphosphatase (ATPase) activity of sarcoplasmic reticulum (SR) was significantly decreased in C. In PC and Ni, this activity was significantly maintained; however, in Gl + PC and Gl + Ni, it was similar to that in C. State III respiration of mitochondria showed similarity to the changes in SR. These results indicated that the K(ATP) channel opener enhanced the effects of ischemic preconditioning, and its blockade abolished these phenomena. We conclude that the ATP-sensitive potassium channel may play one of key roles in the mechanisms of ischemic preconditioning in the dog model.
Geshi
E
E
Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Ishioka
H
H
Nomizo
A
A
Nakatani
M
M
Katagiri
T
T
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008565:Membrane Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D020108:Nicorandil / Q000494:pharmacology; D015221:Potassium Channels; D012039:Regional Blood Flow / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D014475:Uncoupling Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004140:Dinitrophenols; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D015221:Potassium Channels; D014475:Uncoupling Agents; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; D000251:Adenosine Triphosphatases; D000252:Calcium-Transporting ATPases; D005905:Glyburide