English
TitleFasudil Administered during Early Reperfusion Protects against Myocardial Infarction through Activation of PI3K/Akt/NOS Pathway in Rats
Subtitle
AuthorsTakuji Maekawa1), Sungsam Cho1), Taiga Ichinomiya1), Shinya Tosaka2), Shuhei Matsumoto1), Itsuko Shibata1), Tetsuya Hara1), Koji Sumikawa1)
Authors(kana)
Organization1)Department of Anesthesiology, Nagasaki University School of Medicine, 2)Department of Anesthesiology, National Hospital Organization Nagasaki Medical Center
JournalCirculation Control
Volume33
Number2
Page96-103
Year/Month2012/8
ArticleOriginal article
PublisherJapan Society of Circulation Control in Medicine
Abstract[Abstract] Purpose: The authors examined whether fasudil, a Rho-kinase inhibitor, administered during reperfusion could protect the heart against myocardial infarction and, if so, whether phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK1/2), and nitric oxide synthase (NOS) pathways would be involved in the mechanism. Methods: All rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Rats received fasudil at the beginning of reperfusion, or at 30 min after reperfusion. In other groups, rats received fasudil after administration of wortmannin. a PI3K inhibitor, PD98059, an ERK1/2 inhibitor, or N(ƒÖ)-nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor. Results: Fasudil at the beginning of reperfusion (22}9%), but not at 30 min (42}12%) after reperfusion reduced infarct size as compared to the control group (42}7%). The beneficial effect of fasudil was blocked by wortmannin (36}9%) or L-NAME (47}6%), but not PD98059 (26}8%). Conclusions: Fasudil administered early reperfusion protects the heart against myocardial infarction in anesthetized rats, and that this beneficial effect is mediated through PI3K and NOS, but not ERK1/2 activation.
PracticeBasic medicine
KeywordsRho-kinase inhibitor, fasudil, ischemia reperfusion injury, myocardial infarction

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