Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2006-09, Vol.291 (3), p.H1138-H1146

Ort / Verlag

United States

Erscheinungsjahr

2006

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 1 Department of Medical Engineering and Systems Cardiology and 2 Division of Nephrology and Rheumatology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki; 3 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai; 4 Department of Physiology, Tokai University School of Medicine, Isehara; and 5 Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Suita, Japan Submitted 22 February 2006 ; accepted in final form 18 April 2006 We have recently demonstrated that endogenous H 2 O 2 plays an important role in coronary autoregulation in vivo. However, the role of H 2 O 2 during coronary ischemia-reperfusion (I/R) injury remains to be examined. In this study, we examined whether endogenous H 2 O 2 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 N G -monomethyl- L -arginine ( L -NMMA), catalase (a decomposer of H 2 O 2 ), 8-sulfophenyltheophylline (8-SPT, an adenosine receptor blocker), L -NMMA + catalase, L -NMMA + tetraethylammonium (TEA, an inhibitor of large-conductance Ca 2+ -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 H 2 O 2 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 H 2 O 2 , in cooperation with NO, plays an important cardioprotective role in coronary I/R injury in vivo. endothelium-derived relaxing factor; myocardial infarction; vascular endothelial function Address for reprint requests and other correspondence: T. Yada, Dept. of Medical Engineering and Systems Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan (e-mail: yada{at}me.kawasaki-m.ac.jp )