Cardioprotective role of endogenous hydrogen peroxide during ischemia-reperfusion injury in canine coronary microcirculation in vivo

Toyotaka Yada, Hiroaki Shimokawa, Osamu Hiramatsu, Yoshisuke Haruna, Yoshitaka Morita, Naoki Kashihara, Yoshiro Shinozaki, Hidezo Mori, Masami Goto, Yasuo Ogasawara, Fumihiko Kajiya

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Abstract

We have recently demonstrated that endogenous H2O2 plays an important role in coronary autoregulation in vivo. However, the role of H2O2 during coronary ischemia-reperfusion (I/R) injury remains to be examined. In this study, we examined whether endogenous H 2O2 also plays a protective role in coronary I/R injury in dogs in vivo. Canine subepicardial small coronary arteries (≥100 μm) and arterioles (<100 μm) were continuously observed by an intravital microscope during coronary I/R (90/60 min) under cyclooxygenase blockade (n = 50). Coronary vascular responses to endothelium-dependent vasodilators (ACh) were examined before and after I/R under the following seven conditions: control, nitric oxide (NO) synthase (NOS) inhibitor NG-monomethyl-L- arginine (L-NMMA), catalase (a decomposer of H2O2), 8-sulfophenyltheophylline (8-SPT, an adenosine receptor blocker), L-NMMA + catalase, L-NMMA + tetraethylammonium (TEA, an inhibitor of large-conductance Ca2+-sensitive potassium channels), and L-NMMA + catalase + 8-SPT. Coronary I/R significantly impaired the coronary vasodilatation to ACh in both sized arteries (both P < 0.01); L-NMMA reduced the small arterial vasodilatation (both P < 0.01), whereas it increased (P < 0.05) the ACh-induced coronary arteriolar vasodilatation associated with fluorescent H2O2 production after I/R. Catalase increased the small arterial vasodilatation (P < 0.01) associated with fluorescent NO production and increased endothelial NOS expression, whereas it decreased the arteriolar response after I/R (P < 0.01). L-NMMA + catalase, L-NMMA + TEA, or L-NMMA + catalase + 8-SPT further decreased the coronary vasodilatation in both sized arteries (both, P < 0.01). L-NMMA + catalase, L-NMMA + TEA, and L-NMMA + catalase + 8-SPT significantly increased myocardial infarct area compared with the other four groups (control, L-NMMA, catalase, and 8-SPT; all, P < 0.01). These results indicate that endogenous H2O2, in cooperation with NO, plays an important cardioprotective role in coronary I/R injury in vivo.

Original languageEnglish
Pages (from-to)H1138-H1146
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number3
DOIs
Publication statusPublished - 2006

Keywords

  • Endothelium-derived relaxing factor
  • Myocardial infarction
  • Vascular endothelial function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Yada, T., Shimokawa, H., Hiramatsu, O., Haruna, Y., Morita, Y., Kashihara, N., Shinozaki, Y., Mori, H., Goto, M., Ogasawara, Y., & Kajiya, F. (2006). Cardioprotective role of endogenous hydrogen peroxide during ischemia-reperfusion injury in canine coronary microcirculation in vivo. American Journal of Physiology - Heart and Circulatory Physiology, 291(3), H1138-H1146. https://doi.org/10.1152/ajpheart.00187.2006