Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury
Open Access
- 15 February 2004
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 61 (3) , 548-558
- https://doi.org/10.1016/j.cardiores.2003.12.004
Abstract
Objective: To investigate the role of Rho A and Rho-kinase in acute myocardial ischemia/reperfusion injury and the protective effect of Rho-kinase inhibitor, Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide]. Methods and results: Male CD1 mice were subjected to 30 min of coronary occlusion and 24 h reperfusion. Ischemia/reperfusion upregulated expression of Rho A in ischemic myocardium, and subsequently activated Rho-kinase. Y-27632 significantly inhibited the activation of Rho-kinase following ischemia/reperfusion. Treatment with Y-27632 at 10 and 30 mg/kg oral administration, reduced infarct size by 30.2% and 41.1%, respectively (PPPPConclusions: These results suggest that Rho-kinase plays a pivotal role in myocardial ischemia/reperfusion injury. The cardiac protection provided by treatment with a selective Rho-kinase inhibitor is likely via anti-apoptotic effect and attenuation of ischemia/reperfusion-induced inflammatory responses. The finding of this study suggest a novel therapeutic approach to the treatment of acute myocardial ischemia/reperfusion injury.Keywords
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