Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

• Wakahara Nobuyuki

  Division of Cardiology, Department of Internal Medicine III

• Katoh Hideki

  Division of Cardiology, Department of Internal Medicine III

• Yaguchi Yasuhiro

  Division of Cardiology, Department of Internal Medicine III

• Uehara Akihiko

  Division of Cardiology, Department of Internal Medicine III

• Satoh Hiroshi

  Division of Cardiology, Department of Internal Medicine III

• Terada Hajime

  Division of Cardiology, Department of Internal Medicine III

• Fujise Yutaka

  Department of Chemistry, Hamamatsu University School of Medicine

• Hayashi Hideharu

  Division of Cardiology, Department of Internal Medicine III

抄録

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). Methods and 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 ³¹P 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. (Circ J 2004; 68: 156 - 162)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 68 (2), 156-162, 2004

  一般社団法人 日本循環器学会

キーワード

• ATP-sensitive potassium channel
• High-energy phosphates
• Intracellular pH
• Mitochondria
• Reactive oxygen species

詳細情報

• CRID: 1390282680080533376
• NII論文ID: 110002667499
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.68.156
• ISSN: 13474820
• ISSN: 13469843
• ISSN: http://id.crossref.org/issn/13469843
• HANDLE: 10271/1884
• PubMed: 14745152
• Web Site: https://hama-med.repo.nii.ac.jp/records/1851
• Web Site: http://www.jstage.jst.go.jp/article/circj/68/2/68_2_156/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006278083
• 本文言語コード: en
• データソース種別:
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  • IRDB
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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