Abstract | OBJECTIVE: 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 (P<0.01 vs. vehicle). Y-27632 also enhanced post- ischemia cardiac function. Left ventricular systolic pressure, +dP/dt and -dP/dt were significantly improved by 23.5%, 52.3%, and 59.4%, respectively (P<0.01 vs. vehicle). Moreover, Y-27632 reduced ischemia/reperfusion-induced myocardial apoptosis. The apoptotic myocytes in ischemic myocardium after 4 h reperfusion were reduced from 13.1% in vehicle group to 6.4% in Y-27632-treated group (P<0.01). Meanwhile, ischemia/reperfusion-induced downregulation of Bcl-2 in myocardium was remarkably attenuated in the treated animals. Ischemia/reperfusion resulted in remarkable elevation in serum levels of proinflammatory cytokines, interleukin-6 (IL-6), keratinocyte chemoattractant (KC) and granulocyte colony-stimulating factor ( G-CSF), which was significantly suppressed by Y-27632. In addition, Y-27632 decreased ischemia/reperfusion-induced accumulation of neutrophils in the heart by 45% (P<0.01). CONCLUSIONS:
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Authors | Weike Bao, Erding Hu, Ling Tao, Rogely Boyce, Rosanna Mirabile, Douglas T Thudium, Xin-ling Ma, Robert N Willette, Tian-li Yue |
Journal | Cardiovascular research
(Cardiovasc Res)
Vol. 61
Issue 3
Pg. 548-58
(Feb 15 2004)
ISSN: 0008-6363 [Print] England |
PMID | 14962485
(Publication Type: Journal Article)
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Chemical References |
- Amides
- Intracellular Signaling Peptides and Proteins
- Proto-Oncogene Proteins c-bcl-2
- Pyridines
- Y 27632
- Protein Serine-Threonine Kinases
- rho-Associated Kinases
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Topics |
- Amides
(therapeutic use)
- Animals
- Apoptosis
- Blotting, Western
(methods)
- Immunohistochemistry
(methods)
- Intracellular Signaling Peptides and Proteins
- Male
- Mice
- Mice, Inbred Strains
- Myocardial Contraction
(drug effects)
- Myocardial Ischemia
(drug therapy, enzymology, pathology)
- Myocardial Reperfusion Injury
(pathology, prevention & control)
- Myocardium
(enzymology, pathology)
- Neutrophils
(immunology)
- Protein Serine-Threonine Kinases
(analysis, antagonists & inhibitors)
- Proto-Oncogene Proteins c-bcl-2
(analysis)
- Pyridines
(therapeutic use)
- rho-Associated Kinases
|