Effect of Angiotensin II Type 1 Receptor Blocker on Cardiac Angiotensin-Converting Enzyme and Chymase-Like Activities, and Cardiac Fibrosis in Cardiomyopathic Hamsters

Journal of Veterinary Medical Science

Kensuke ORITO¹  Miki SHIMIZU²  Mizuho UCHIDA²  Shunsuke SHIMAMURA²  Ryou TANAKA²  Yoshihisa YAMANE² 

[1] Department of Veterinary Pharmacology, Azabu University School of Veterinary Medicine;Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology

关键词: angiotensin-converting enzyme;    chymase;    heart failure;    remodeling;    renin-angiotensin system;   

DOI  :  10.1292/jvms.68.227

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(24)Cited-By(3)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.

【 授权许可】

Unknown