Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism
The objective of our study was to investigate the effect of Aliskiren, a renin inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats underwent right nephrectomy and were randomly assigned into 3 gr...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2012-05-01
|
Series: | Bosnian Journal of Basic Medical Sciences |
Subjects: | |
Online Access: | http://www.bjbms.org/ojs/index.php/bjbms/article/view/2498 |
id |
doaj-6cb56546f82445b481926d36ce8a71cc |
---|---|
record_format |
Article |
spelling |
doaj-6cb56546f82445b481926d36ce8a71cc2020-11-24T23:16:26ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBosnian Journal of Basic Medical Sciences1512-86011840-48122012-05-0112210.17305/bjbms.2012.2498290Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanismLikun Ma0Jinsheng Hua1Lifeng He2Qian Li3Junling Zhou4Jiangtao Yu5Department of Cardiology, Anhui Provincial HospitalDepartment of Cardiology, Anhui Provincial HospitalDepartment of Cardiology, Anhui Provincial HospitalDepartment of Cardiology, Anhui Provincial HospitalDepartment of Cardiology, Anhui Provincial HospitalDepartment of Cardiology, Zentralklinik Bad Berka GmbHThe objective of our study was to investigate the effect of Aliskiren, a renin inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats underwent right nephrectomy and were randomly assigned into 3 groups: control group (CON group: silicone tube was embedded subcutaneously); DOCA treated group (DOC group: 200 mg of DOCA was subcutaneously administered); DOCA and Aliskiren (ALI) treated group (ALI group: 200 mg of DOCA and 50 mg/kg/d ALI were subcutaneously and intragastrically given, respectively). Treatment was done for 4 weeks. Sirius red staining was employed to detect the expression of myocardial collagen, and the myocardial collagen volume fraction (CVF) and perivascular collagen volume area (PVCA) were calculated. Radioimmunoassay was carried out to measure the renin activity (RA) and content of angiotensin II (Ang II) in the plasma and ventricle. Western blot assay was done to detect the expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (PERK1/2) and matrix metalloproteinase 9 (MMP-9). In the DOC group and ALI group, the CVF and PVCA were significantly increased; the RA and Ang II levels in the plasma and ventricle were remarkably lowered when compared with the CON group. The RA and Ang II levels in the ventricle of the ALI group were significantly lower than those in the DOC group. Moreover, the expressions of ERK1/2, PERK1/2 and MMP9 were the lowest in the CON group, but those in the ALI group were significantly reduced as compared to the DOC group. ALI can inhibit the DOCA induced myocardial fibrosis independent of its pressure-lowing effect, which may be related to the suppression of RA and Ang II production, inhibition of ERK1/2 phosphorylation and MMP9 expression in the heart.http://www.bjbms.org/ojs/index.php/bjbms/article/view/2498Aliskirendeoxycorticosteronemyocardial fibrosisrenin- angiotensin - aldosterone system |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Likun Ma Jinsheng Hua Lifeng He Qian Li Junling Zhou Jiangtao Yu |
spellingShingle |
Likun Ma Jinsheng Hua Lifeng He Qian Li Junling Zhou Jiangtao Yu Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism Bosnian Journal of Basic Medical Sciences Aliskiren deoxycorticosterone myocardial fibrosis renin- angiotensin - aldosterone system |
author_facet |
Likun Ma Jinsheng Hua Lifeng He Qian Li Junling Zhou Jiangtao Yu |
author_sort |
Likun Ma |
title |
Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
title_short |
Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
title_full |
Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
title_fullStr |
Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
title_full_unstemmed |
Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
title_sort |
anti-fibrotic effect of aliskiren in rats with deoxycorticosterone induced myocardial fibrosis and its potential mechanism |
publisher |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
series |
Bosnian Journal of Basic Medical Sciences |
issn |
1512-8601 1840-4812 |
publishDate |
2012-05-01 |
description |
The objective of our study was to investigate the effect of Aliskiren, a renin inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats underwent right nephrectomy and were randomly assigned into 3 groups: control group (CON group: silicone tube was embedded subcutaneously); DOCA treated group (DOC group: 200 mg of DOCA was subcutaneously administered); DOCA and Aliskiren (ALI) treated group (ALI group: 200 mg of DOCA and 50 mg/kg/d ALI were subcutaneously and intragastrically given, respectively). Treatment was done for 4 weeks. Sirius red staining was employed to detect the expression of myocardial collagen, and the myocardial collagen volume fraction (CVF) and perivascular collagen volume area (PVCA) were calculated. Radioimmunoassay was carried out to measure the renin activity (RA) and content of angiotensin II (Ang II) in the plasma and ventricle. Western blot assay was done to detect the expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (PERK1/2) and matrix metalloproteinase 9 (MMP-9). In the DOC group and ALI group, the CVF and PVCA were significantly increased; the RA and Ang II levels in the plasma and ventricle were remarkably lowered when compared with the CON group. The RA and Ang II levels in the ventricle of the ALI group were significantly lower than those in the DOC group. Moreover, the expressions of ERK1/2, PERK1/2 and MMP9 were the lowest in the CON group, but those in the ALI group were significantly reduced as compared to the DOC group. ALI can inhibit the DOCA induced myocardial fibrosis independent of its pressure-lowing effect, which may be related to the suppression of RA and Ang II production, inhibition of ERK1/2 phosphorylation and MMP9 expression in the heart. |
topic |
Aliskiren deoxycorticosterone myocardial fibrosis renin- angiotensin - aldosterone system |
url |
http://www.bjbms.org/ojs/index.php/bjbms/article/view/2498 |
work_keys_str_mv |
AT likunma antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism AT jinshenghua antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism AT lifenghe antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism AT qianli antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism AT junlingzhou antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism AT jiangtaoyu antifibroticeffectofaliskireninratswithdeoxycorticosteroneinducedmyocardialfibrosisanditspotentialmechanism |
_version_ |
1725587359825657856 |