[Effects of angiotensin II receptor antagonism on matrix metalloproteinases and fibronectin in rats with experimental myocardial infarction].
OBJECTIVE
To investigate the effects of angiotensin II (AngII) receptor (AT(1), AT(2)) antagonists on myocardial matrix metalloproteinases (MMPs) and fibronectin (FN) in rats with myocardial infarction (MI).


METHODS
Rat MI was induced by permanent ligation of the left coronary artery. Placebo, AT(1) receptor antagonist valsartan (10 mgxkg(-1)xd(-1)) or AT(2) receptor antagonist PD123319 (30 mgxkg(-1)xd(-1)) were given 7 days prior MI surgery. On the 1st, 3rd and 7th day after MI, Expressions of MMP-2, 3, 9, tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and FN at protein level were determined by Western blot in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricular (RV). Myocardial FN distribution was also assayed by immunofluorescence.


RESULTS
Typical myocardial remodeling was shown in IS and LVFW 7 days after MI. MMP-2, 3, 9 expressions at protein level were significantly increased whereas TIMP-1 and FN expressions significantly decreased in IS 1, 3, 7 days post MI in a time-dependent manner compared to that of sham operated hearts. MMP-2, 3, 9 expressions was significantly increased and TIMP-1 and FN expression significantly decreased in LVFW at the 1st post MI day and maintained up to 7th post MI day compared to that of sham operated hearts. Up-regulated expressions of MMP-2, 3, 9 and down-regulated TIMP-1 and FN expressions in IS and LVFW could be significantly attenuated by valsartan but not by PD123319. Valsartan but not PD123319 also significantly reduced MI sizes (40.4% +/- 2.1% vs 49.5% +/- 2.1%, P < 0.05).


CONCLUSIONS
AT(1) receptor antagonist involves in the pathology procession of myocardial remodeling and might lead to the development and progression of congestive heart failure by the increasing expressions of MMP-2, 3, 9, which contribute to degradative extracellular matrix FN in myocardium.
Zhang
Xin
X
Department of Cardiology, General Military Hospital of Chengdu, Chengdu 610083, China.
Yang
Yong-jian
YJ
Zhu
Wen-ling
WL
Huang
Yan
Y
Zhu
Zhi-ming
ZM
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D005353:Fibronectins / Q000096:biosynthesis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D047228:Angiotensin II Type 1 Receptor Blockers; D005353:Fibronectins; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9