Document Detail

Effect of Angiotensin II Type 1 receptor blocker on cardiac angiotensin-converting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters.
MedLine Citation:
PMID:  16598165     Owner:  NLM     Status:  MEDLINE    
It has been reported that cardiac chymase has an effect on cardiac fibrosis through the Angiotensin (Ang) II formation and an Ang II-independent mechanism. In the present study, Ang II type 1 (AT1) receptor blocker (candesartan cilexetil) was administered to dilated cardiomyopathic (DCM; Bio TO2) hamsters for 4 weeks to study the effect of AT1 receptor blocker on cardiac chymase-like activity and cardiac fibrosis. Echocardiography, histological examination, and assessment of cardiac angiotensin-converting enzyme (ACE)/chymase-like activities were conducted. Hamsters showed cardiac dysfunction due to increased left ventricular dimensions and decreased ventricular wall thickness, significant increase in cardiac chymase-like activity, and fibrosis. This result indicates that the cardiac chymase-like activity is responsible for cardiac fibrosis. When candesartan cilexetil was administered to Bio TO2 hamsters, cardiac chymase-like activity increased significantly, whereas cardiac fibrosis decreased significantly. Cardiac ACE and chymase-like activities were unchanged in non-DCM hamsters with candesartan cilexetil. This suggests that the cardiac Ang II formation mechanism was stimulated by suppressing the effect of cardiac Ang II, and cardiac chymase-like activity could be increased. Moreover, this mechanism may be more highly activated if cardiac Ang II is activated in the heart. In conclusion, we demonstrated that AT1 receptor blocker reduced cardiac fibrosis, although cardiac chymase-like activity increased. Because the Ang II-forming pathway and the effect of chymase in hamsters is similar to that in dogs, the results of the present study may supplement the available information for dogs.
Miki Shimizu; Ryou Tanaka; Mizuho Uchida; Kensuke Orito; Shunsuke Shimamura; Yoshihisa Yamane
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of veterinary medical science / the Japanese Society of Veterinary Science     Volume:  68     ISSN:  0916-7250     ISO Abbreviation:  J. Vet. Med. Sci.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-04-06     Completed Date:  2006-05-11     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9105360     Medline TA:  J Vet Med Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  227-33     Citation Subset:  IM    
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchushi, Tokyo 183-0054, Japan.
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers / pharmacology*,  therapeutic use
Benzimidazoles / pharmacology*,  therapeutic use
Biphenyl Compounds / pharmacology*,  therapeutic use
Body Weight / drug effects
Cardiomyopathy, Dilated / drug therapy*,  enzymology,  pathology,  veterinary*
Endomyocardial Fibrosis / drug therapy*,  enzymology,  pathology,  veterinary*
Heart Ventricles / pathology
Myocardium / enzymology
Organ Size / drug effects
Peptidyl-Dipeptidase A / metabolism*
Random Allocation
Serine Endopeptidases / metabolism*
Tetrazoles / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Biphenyl Compounds; 0/Tetrazoles; EC A; EC 3.4.21.-/Serine Endopeptidases; EC; R85M2X0D68/candesartan cilexetil

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