Mechanisms of losartan for inhibition of myocardial fibrosis following myocardial infarction in rats.
- Author:
Zhen-li WU
1
;
Ding-li XU
;
Lie-hua DENG
;
Yong-wei WEN
;
Peng HUANG
;
Shu-chang BAI
;
Liang SU
Author Information
- Publication Type:Journal Article
- MeSH: Aldosterone; metabolism; Angiotensin II; metabolism; Angiotensin II Type 1 Receptor Blockers; therapeutic use; Animals; Fibrosis; etiology; prevention & control; Losartan; therapeutic use; Male; Myocardial Infarction; drug therapy; metabolism; Myocardium; pathology; RNA, Messenger; genetics; metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; genetics; metabolism
- From: Journal of Southern Medical University 2008;28(12):2260-2263
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of losartan on cardiac mineralocorticoid receptor (MR) mRNA in rats after acute myocardial infarction (AMI).
METHODAMI was induced in male SD rats by ligation of the left coronary artery. The survived rats were randomly divided into AMI group, losartan group, and sham-operated group. The cardiac functions of the rats were assessed by echocardiogram and hemodynamics, and the contents of angiotensin II (Ang II) and aldosterone (Ald) in the myocardial tissues were determined by radioimmunoassay. The collagen density in the myocardial tissues were calculated by Masson's trichrome staining and the expression of MR mRNA were determined by real-time quantitative fluorescent PCR.
RESULTSBoth the contents of AngII and Ald in the myocardial tissues increased significantly in AMI group compared with those in the sham-operated group (P<0.01). The expression of MR mRNA and collagen density in the myocardial tissues also increased significantly than that in sham-operated group (P<0.01). After four weeks of losartan treatment, the contents of AngII and Ald in the myocardial tissues decreased significantly (P<0.05) and the expression of MR mRNA was also considerably lowered (P<0.01) in comparison with those in the AMI group. Treatment with losartan also resulted in significant decrease of the collagen density in the myocardial tissues.
CONCLUSIONSLosartan may reduce reactive fibrosis not only by attenuating the Ald signaling pathway but also by decreasing the expression of MR.