Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters
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概要
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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.
著者
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Orito Kensuke
Department of Physiology II, School of Veterinary Medicine, Azabu University
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Yamane Yoshihisa
Department Of Veterinary Surgery Tokyo University Of Agriculture And Technology
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Shimizu Miki
Department Of Food And Human Health Sciences Graduate School Of Human Life Science Osaka City Univer
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TANAKA Ryou
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology
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SHIMAMURA Shunsuke
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology
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TANAKA Ryou
Department of Veterinary Surgery, Faculth of Agriculture, Tokyo University of Agriculture and Technology
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UCHIDA Mizuho
Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology
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SHIMAMURA Shunsuke
Department of Veterinary Surgery, Faculth of Agriculture, Tokyo University of Agriculture and Technology
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Orito Kensuke
Department of Pharmacology, Tohoku University School of Medicine
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ORITO Kensuke
Department of Pharmacology, Azabu University School of Veterinary Medicine
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