Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts.
BACKGROUND
Recent studies have implicated the opening of mitochondrial K(ATP) (mitoK(ATP)) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC).


RESULTS
The involvement of mitoK(ATP) channels and ROS in the cardioprotective effects of both IPC and the mitoK(ATP) channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pH(i)) were also examined using (31)P nuclear magnetic resonance spectroscopy. Although both the mitoK(ATP) channel inhibitor 5-hydroxydecanoate and the antioxidant N-acetylcysteine abolished the postischemic recovery of contractile function by DZ, neither of them inhibited that by IPC. IPC attenuated the decline in pHi during ischemia, but DZ did not (6.28+/-0.04 in IPC, p<0.05, and 6.02+/-0.05 in DZ vs 6.02 +/-0.06 in control hearts). DZ, but not IPC, reduced the decrease in ATP levels during ischemia (ATP levels at 20-min ischemia: 26.3+/-3.4% of initial value in DZ, p<0.05, and 8.1+/-3.0% in IPC vs 15.1+/-1.3% in control hearts).


CONCLUSIONS
These results suggest that DZ-induced cardioprotection is related to ROS production and reduced ATP degradation during ischemia, whereas attenuated acidification during ischemia is involved in IPC-induced cardioprotection, which is not mediated through mitoK(ATP) channel opening or ROS production.
Wakahara
Nobuyuki
N
Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine, Japan.
Katoh
Hideki
H
Yaguchi
Yasuhiro
Y
Uehara
Akihiko
A
Satoh
Hiroshi
H
Terada
Hajime
H
Fujise
Yutaka
Y
Hayashi
Hideharu
H
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology*; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D008279:Magnetic Resonance Imaging; D008297:Male; D024101:Mitochondrial Proteins; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D010759:Phosphorus Isotopes; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D002316:Cardiotonic Agents; D054086:KATP Channels; D024101:Mitochondrial Proteins; D010759:Phosphorus Isotopes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017382:Reactive Oxygen Species; C092520:uK-ATP-1 potassium channel; D003981:Diazoxide