Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury

• Published in: Cardiovascular research 2004-02, Vol.61 (3), p.548-558
• Main Authors: BAO, Weike, HUB, Erding, LING TAO, BOYCE, Rogely, MIRABILE, Rosanna, THUDIUMD, Douglas T, MA, Xin-Ling, WILLETTEA, Robert N, YUEA, Tian-Li
• Format: Article
• Language: English
• Subjects: Amides - therapeutic use; Animals; Apoptosis; Biological and medical sciences; Blotting, Western - methods; Cardiology. Vascular system; Coronary heart disease; Heart; Immunohistochemistry - methods; Intracellular Signaling Peptides and Proteins; Male; Medical sciences; Mice; Mice, Inbred Strains; Myocardial Contraction - drug effects; Myocardial Ischemia - drug therapy; Myocardial Ischemia - enzymology; Myocardial Ischemia - pathology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - enzymology; Myocardium - pathology; Neutrophils - immunology; Protein-Serine-Threonine Kinases - analysis; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - analysis; Pyridines - therapeutic use; rho-Associated Kinases
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2003.12.004

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]. 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 (P