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Title: Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure

Author
item MORGAN, ERIC - CASE WESTERN RESERVE UNIV
item Young, Martin
item MCELFRESH, TRACY - CASE WESTERN RESERVE UNIV
item KUNG, THEODORE - CASE WESTERN RESERVE UNIV
item HOIT, BRIAN - CASE WESTERN RESERVE UNIV
item CHANDLER, MARGARET - CASE WESTERN RESERVE UNIV
item STANLEY, WILLIAM - CASE WESTERN RESERVE UNIV

Submitted to: Fundamental and Clinical Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/25/2006
Publication Date: 10/20/2006
Citation: Morgan, E.E., Young, M.E., Mcelfresh, T.A., Kung, T.A., Hoit, B.D., Chandler, M.P., Stanley, W.C. 2006. Chronic treatment with trimethzidine reduces the upregulation of atrial natriuretic peptide in heart failure. Fundamental and Clinical Pharmacology. 20(5):503-505.

Interpretive Summary: The prevalence of heart failure (a form of heart disease in which heart function is severely diminished) is increasing at an alarming rate in the United States. The mechanisms responsible for abnormal heart function during heart failure are currently poorly understood. Previous studies have suggested that the failing heart has increased oxidative stress (i.e., produces highly reactive oxidants, such as the free radical superoxide), which in turn damages the heart. The present study investigated the potential mechanisms by which the heart produces superoxide. The results strongly suggest that activation of specific proteins in the failing heart (such as glucose-6-phosphate dehydrogenase) causes production of superoxide.

Technical Abstract: Trimetazidine (TMZ) is effective for the treatment of ischemic cardiomyopathy; however, little is known about the effect of TMZ in established injury-induced heart failure. When rats with established infarct-induced heart failure were treated for 12 weeks with TMZ there was no effect on left ventricular function or dilation, or on mRNA expression of fatty acid oxidation enzymes. On the other hand, TMZ significantly reduced atrial natriuretic peptide mRNA levels compared with untreated rats.