[Mechanisms of losartan for inhibition of myocardial fibrosis following myocardial infarction in rats].
OBJECTIVE
To investigate the effect of losartan on cardiac mineralocorticoid receptor (MR) mRNA in rats after acute myocardial infarction (AMI).


METHODS
AMI 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.


RESULTS
Both 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.


CONCLUSIONS
Losartan may reduce reactive fibrosis not only by attenuating the Ald signaling pathway but also by decreasing the expression of MR.
Wu
Zhen-li
ZL
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. dinglixu@fimmu.com
Xu
Ding-li
DL
Deng
Lie-hua
LH
Wen
Yong-wei
YW
Huang
Peng
P
Bai
Shu-chang
SC
Su
Liang
L
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D000450:Aldosterone; D019808:Losartan