Fasudil Administered during Early Reperfusion Protects against Myocardial Infarction through Activation of PI3K/Akt/NOS Pathway in Rats

抄録

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(ω)-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.