| p38 alpha mitogen-activated protein kinase inhibition improves cardiac function and reduces myocardial damage in isoproterenol-induced acute myocardial injury in rats. | |
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MedLine Citation:
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PMID: 15454858 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p38 mitogen-activated protein (MAP) kinase is activated during ischemic/hypoxic myocardial injury. However, the role of activated p38 MAP kinase on cardiac function after myocardial injury is not well understood. In the present study, we investigated the cardioprotective effects of p38 MAP kinase inhibition in a rat model of acute myocardial injury, induced by subcutaneous injection of isoproterenol (ISO, 20 mg/kg/d for 3 days). A synthetic p38 alpha MAP kinase inhibitor, SD-282 (40 mg/kg) or vehicle (0.25% Tween 80 in saline) was given intraperitoneally twice a day for 3 days, concomitant with ISO treatment. Cardiac function, systolic blood pressure, gene expression including collagen I and III, fibronectin and COX-2, and the myocardial injury were analyzed. Results showed that administration of SD-282 remarkably improved ISO-induced reduction of cardiac function with increases in ejection fraction (P < 0.001), cardiac output (P < 0.05), stroke volume (P < 0.001), and cardiac index (P < 0.01). SD-282 abolished ISO-induced reduction of systolic blood pressure (106.7 +/- 2.2 versus 123.1 +/- 5.3 mm Hg, P < 0.05). The ISO-induced expression of COX-2, collagen I and III, and fibronectin genes was reduced significantly (P < 0.05 in all cases) by administration of SD-282. The myocardial injury induced by ISO was significantly reduced by the treatment of SD-282 as judged by the reduction of myocardial necrosis. Data suggest that p38 alpha MAP kinase may be involved in the pathogenesis of cardiac dysfunction in ischemic myocardial injury. Inhibition of this enzyme may improve cardiac function and protect myocardium from ischemic/hypoxic injury that occurs during ischemic heart disease. |
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Authors:
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Zhihe Li; Thomas-Toan Tran; Jing Ying Ma; Gilbert O'Young; Ann M Kapoun; Sarvajit Chakravarty; Sundeep Dugar; George Schreiner; Andrew A Protter |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 44 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-29 Completed Date: 2005-06-14 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 486-92 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Preclinical Research, Scios Inc., Fremont, CA 94555, USA. li@sciosinc.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Blood Pressure / drug effects Body Weight / drug effects Cardiotonic Agents / pharmacology Gene Expression / drug effects Injections, Intraperitoneal Isoproterenol Male Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors* Myocardial Ischemia / etiology, physiopathology, prevention & control* Myocardium / metabolism, pathology Necrosis Organ Size / drug effects Phenotype Polymerase Chain Reaction RNA, Messenger / biosynthesis Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/RNA, Messenger; 7683-59-2/Isoproterenol; EC 2.7.11.24/Mitogen-Activated Protein Kinase 14 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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