ABSTRACT. 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. KEY WORDS: angiotensin-converting enzyme, chymase, heart failure, remodeling, renin-angiotensin system. J. Vet. Med. Sci. 68(3): 227-233, 2006 The renin-angiotensin system (RAS) is an adaptive mechanism of the body that maintains circulatory homeostasis and cardiac function in the presence of excessive hemodynamic overload. Although it has been thought that RAS exists only in the circulatory system (circulating RAS), RAS also has been found to exist in the heart (cardiac RAS) [14,24]. Angiotensin (Ang) II, one of the effector peptides of RAS, is known as a causative agent of cardiac remodeling [15]. The Ang II-forming mechanism in the dog's heart is the same as that in humans. In both dogs and humans, cardiac Ang II is produced not only by the cardiac angiotensinconverting enzyme (ACE)-dependent pathway, but also by the cardiac chymase-dependent pathway [1,2,23]. The presence of this alternative pathway indicates that ACE inhibitors cannot completely inhibit the cardiac Ang II. A study in rats revealed that Ang II type 1 (AT1) receptor blockers reduced the hemodynamic load and cardiac remodeling by inhibiting the effect of Ang II at the receptor level, and consequently improved cardiac function [20]. Due to this difference in the effector site, AT1 receptor blockers are expected to be more superior to ACE inhibitors....