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

研究成果: Article査読

43 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)H1138-H1146
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
291
3
DOI
出版ステータスPublished - 2006

ASJC Scopus subject areas

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

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