Document Detail

Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats.
MedLine Citation:
PMID:  16324756     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Daunorubicin is an anthracycline anti-tumor agent; anthracycline chemotherapy in cancer can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure; the first-line treatment is diuretics and digoxin. Recently, angiotensin-converting enzyme inhibitors have been shown to be effective in the treatment of such toxicity. The purpose of this study was to investigate the effects of angiotensin II type-1 receptor antagonist (candesartan) in a rat model of daunorubicin-induced cardiomyopathy.
METHODS: Rats were treated with a cumulative dose of 9 mg/kg body weight daunorubicin (i.v.). 28 days later, after the development of cardiomyopathy, animals were randomly assigned to candesartan-treated (5 mg/kg/day, p.o.) or vehicle-treated groups; age-matched normal rats were used as the control group. Candesartan treatment was continued for 28 days. Hemodynamic and echocardiographic parameters were measured, cardiac protein and mRNA were analyzed, and histopathological analyses of myocardial fibrosis, cell size and apoptosis were conducted.
RESULTS: Following cardiomyopathy, left ventricular end diastolic pressure and left ventricular systolic dimension were significantly elevated; while % fractional shortening and Doppler E/A ratio were significantly reduced. Cardiomyopathic hearts showed significant increases in % fibrosis, % apoptosis, and myocyte diameter/body weight ratio; candesartan treatment reversed these changes. Fas-L protein overexpression in myopathic hearts was significantly suppressed by treatment with candesartan. Moreover, SERCA2 mRNA and protein expression were both down-regulated in myopathic hearts and restored to normal by candesartan treatment, significantly.
CONCLUSIONS: Our findings suggest that candesartan treatment significantly improved the left ventricular function and reversed the myocardial pathological changes investigated in this model of daunorubicin-induced cardiomyopathy; suggesting its potentials in limiting daunorubicin cardiotoxicity.
Mayako Soga; Fadia A Kamal; Kenichi Watanabe; Meilei Ma; Suresh Palaniyandi; Paras Prakash; Punniyakoti Veeraveedu; Sayaka Mito; Megumi Kunisaki; Hitoshi Tachikawa; Makoto Kodama; Yoshifusa Aizawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-12-01
Journal Detail:
Title:  International journal of cardiology     Volume:  110     ISSN:  0167-5273     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-12     Completed Date:  2006-11-13     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  378-85     Citation Subset:  IM    
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Angiotensin II Type 2 Receptor Blockers*
Apoptosis / drug effects
Benzimidazoles / pharmacology*,  therapeutic use
Blood Pressure
Body Weight / drug effects
Calcium-Transporting ATPases / genetics
Cardiomyopathies / chemically induced,  drug therapy*,  metabolism,  physiopathology*
Cytoprotection / drug effects
Daunorubicin / pharmacology*,  therapeutic use
Disease Models, Animal
Fas Ligand Protein
Membrane Glycoproteins / metabolism
Organ Size / drug effects
RNA, Messenger / genetics
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 2 / metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Survival Rate
Tetrazoles / pharmacology*,  therapeutic use
Tumor Necrosis Factors / metabolism
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin II Type 2 Receptor Blockers; 0/Benzimidazoles; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/RNA, Messenger; 0/Receptor, Angiotensin, Type 2; 0/Tetrazoles; 0/Tnfsf6 protein, rat; 0/Tumor Necrosis Factors; 20830-81-3/Daunorubicin; EC protein, rat; EC ATPases; EC Reticulum Calcium-Transporting ATPases; S8Q36MD2XX/candesartan

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