Elucidation of cardiac muscle fibrosis mechanism by renin-angiotensin system through chymase

慢性心力衰竭时，肾素-血管紧张素（RAS）系统增强. RAS系统中存在血管紧张素转换酶和糜酶，这些酶在心力衰竭中可能发挥病理生理作用。在这项研究中，ACE抑制剂（依那普利）和血管紧张素II型受体阻滞剂（ARB：坎地沙坦）对组织RAS的反应进行了检查。对患有主动脉缩窄的仓鼠给予ACE抑制剂和ARB。超声心动图显示ACE抑制剂和ARB组心肌增生明显抑制，心/体重比明显降低。ACE抑制剂和ARB对左心室ACE和糜酶活性无明显抑制作用。而ACE抑制剂和ARB均能降低收缩压和左心室Ang Ⅱ水平，且联合用药时降低幅度更大。提示压力超负荷时，后负荷增加和组织中Ang Ⅱ的增加是导致心肌肥厚的重要因素.

In chronic heart failure, renin- angiotensin (RAS) system is enhanced. Angiotensin converting enzyme and chymase are present in RAS system, and these enzymes may affect pathophysiologically in cardiac failure. In this study, response to tissue RAS of ACE inhibitor (enalapril) and Ang II type receptor blocker (ARB : Candesartan) were examined. Hamsters with an aortic coarctation were given ACE inhibitor and ARB. Cardiac muscle hyperplasia depression was observed in ACE inhibitor and ARB administrated group by echocardiography, and the decrease that was significant in heart / body weight ratio was observed. The left ventricle ACE and the chymase activity were not inhibited by ACE inhibitor and ARB. However, decreased systolic blood pressure and decrease of left ventricle Ang II were observed by ACE inhibitor and ARB, and this tendency was more massive in a combined medication. These results suggested increasing afterload and tissue Ang II contribute cardiac hypertrophy in pressure overload.