title: Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Wakahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Katoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yaguchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Uehara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
authors.forename: Hajime
authors.initials: H
authors.lastname: Terada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujise
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hayashi
mesh_terms: 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
chemical_list: 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