Document Detail

p38 alpha mitogen-activated protein kinase inhibition improves cardiac function and reduces myocardial damage in isoproterenol-induced acute myocardial injury in rats.
MedLine Citation:
PMID:  15454858     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  44     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-29     Completed Date:  2005-06-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  486-92     Citation Subset:  IM    
Department of Pharmacology and Preclinical Research, Scios Inc., Fremont, CA 94555, USA.
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MeSH Terms
Acute Disease
Blood Pressure / drug effects
Body Weight / drug effects
Cardiotonic Agents / pharmacology
Gene Expression / drug effects
Injections, Intraperitoneal
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Myocardial Ischemia / etiology,  physiopathology,  prevention & control*
Myocardium / metabolism,  pathology
Organ Size / drug effects
Polymerase Chain Reaction
RNA, Messenger / biosynthesis
Rats, Wistar
Reg. No./Substance:
0/Cardiotonic Agents; 0/RNA, Messenger; 7683-59-2/Isoproterenol; EC Protein Kinase 14

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