English |
Title | Fasudil Administered during Early Reperfusion Protects against Myocardial Infarction through Activation of PI3K/Akt/NOS Pathway in Rats |
Subtitle | |
Authors | Takuji Maekawa1), Sungsam Cho1), Taiga Ichinomiya1), Shinya Tosaka2), Shuhei Matsumoto1), Itsuko Shibata1), Tetsuya Hara1), Koji Sumikawa1) |
Authors(kana) | |
Organization | 1)Department of Anesthesiology, Nagasaki University School of Medicine, 2)Department of Anesthesiology, National Hospital Organization Nagasaki Medical Center |
Journal | Circulation Control |
Volume | 33 |
Number | 2 |
Page | 96-103 |
Year/Month | 2012/8 |
Article | Original article |
Publisher | Japan 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. |
Practice | Basic medicine |
Keywords | Rho-kinase inhibitor, fasudil, ischemia reperfusion injury, myocardial infarction |