作者机构:
Department of Geriatric Cardiology, Xianya Hospital, Hunan Medical University;Department of Pathology, basic medicine college of Nanhua university;[Xie Xiumei; Yu Guolong] Department of Geriatric Cardiology, Xianya Hospital, Hunan Medical University;[Liang Xiaoqiu] Department of Pathology, basic medicine college of Nanhua university
摘要:
Objective This study was designed to investigate effects of AT_1 receptor antagonist (losartan) and ACF inhibitor (fosinopril) on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left vetnricle of spontaneously hypertensive rats (SHR). Methods This study was performed in 30 SHRs of 16-week-old. The rats were randomized to three groups: SHR-L (losartan, 30 mg·kg~(-1)·d~(-1)), SHR -F (fosinopril, 10 mg·kg~(-1)·d~(-1)), and SHR-C (placebo), eath group consisting of 10 rats. 5 rats randomly obtained from each group were killed at 8 weeks and 16 weeks of te study respectively. The cardiomyocyte apoptosis was examined by in situ TDT-mediated dUTP nick end labeling (TUNEL). The parameters of myocardial fibrosis such as collagen volume fraction (CVF) and perivascular collagen area (PVCA) were determined by pathological examination with computed processing. Ang II concentrations of plasma and myocardium were measured by radioimmunoassay. Results The results showed that: (1) Compared with SHR-C at 8 weeks and 16 weeks systolic blood presure was decreased similarly in the both treatment groups. Left ventricular weight and left ventricular mass indexes were lower significantly in the both treatment groups. The left ventricular mass index at 16 weeks was reduced to a lesser extent in SHR-F group than that in SHR-L group. (2) Compared with SHR-C, the cardiomycyte apoptotic index (APOI) at 8 weeks was reduced significantly only in SHR-F group, and at 16 weeks in both treatment groups. The APOI of SHR-F group was lower than that of SHR-L group at 16 weeks. (3) Compared with SHR-C, CVF and PVCA at 8 weeks and 16 weeks were reduced significantly in the SHRs treated with either fosinopril or losartan. However, CVF at the latter endpoint in the SHR-F was lower than in the SHR-L. (4) Compared with SHR-C, plasma and myocardium Ang II levels at both endpoints were increased significantly in SHR-L. However, plasma Ang II levels were not changed, and myocardium Ang II levels reduced significantly at 8 weeks and 16 weeks in SHR-F group. Conclusion These results indicate that either of losartan and fosinporil effectively inhibits cardiomyocyte apoptosis and myocardial fibrosis, and reverses heart hypertrophy. Fosinopril may be more effective in these cardiprotective effects. The effects of ACEI or AT_1 antagonist on myocardiocyte apoptosis, myocardial fibrosis and left ventricular hypertrophy were related to inhibition of myocardium reninangiotensin system.
作者机构:
[易光辉; 杨永宗] Department of Pathophysiology, Xiangya Medical College, Central South University;[杨保堂; 王佐; 吴孟津; 万载阳; 尹卫东] Institute of Cardiovascular Disease, Nanhua University;Tsinghua Unisplendour Guhan Bio-pharmaceutical Corporation;[胡隆梅] Tsinghua Unisplendour Guhan Bio-pharmaceutical Corporation
作者机构:
Cent S Univ, Xiangya Med Coll, Dept Pathophysiol, Changsha 410078, Peoples R China.;Nanhua Univ, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;[Yuan, ZH] Department of Pathphysiology, Xiangya Medical College, Central South University;[Yang, YZ; Yang, XY] Institute of Cardiovascular Research of Nanhua University
通讯机构:
Department of Pathphysiology, Xiangya Medical College, Central South University, China