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.
|ジャーナル||American Journal of Physiology - Heart and Circulatory Physiology|
|出版ステータス||Published - 2006|
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