Abstract:

Abstract:Objective
To explore the effects of angiotensin Ⅱ(AngⅡ)on the synthesis and release of plasminogen activator inhibitor 1(PAI-1) and tissue plasminogen activator(tPA) through modulating extracellular signal regulated kinase(ERK) activated with AngⅡtype 1 receptor(ATlR) in rats with acute myocardial infarction(AMI). Methods 24 Sprague-Dawley rats were randomly divided into 3 groups:sham operation group(n=8),AMI group(n=8),and PD98059 group(n=8). The rat model of AMI was established by ligating left anterior descend coronary artery. On the 14th day after AMI,the tissue slices of myocardium were prepared and the histopathological changes of myocardium were observed with microscope;the AngⅡ levels in plasma and aortic tissue were measured by radioimmunoassay;the PAI-1 and tPA activities were measured by spectrophotometric assay;the expressions of p-ERK1/2 and ATlR proteins in the homogenized aortic tissue were examined by Western blotting in rats in various groups.Results ①The HE-dyed tissue slices of myocardium showed that the myocardium was normal(cardiac muscle fibers to line up in order and nucleus being rule) in sham operation group but abnormal(the disruption,cavity and dissolution of cardiac muscle fibers,the lysis of nucleus,the proliferation of fibrous connective tissue and the infiltration of inflammatory cells) in AMI group,and  the damaged myocardium after AMI was remarkably improved in PD98059 group. ② Compared with sham operation group，the AngⅡlevels and PAI-1 activities in plasma and incubation solution for aorta were significantly increased(all P<0.05)，but the activity of tPA and the ratio of tPA to PAI-1 in plasma and incubation solution for aorta were decreased remarkably in AMI group(all P<0.05). ③Compared with sham operation group，the expressions of p-ERK1/2 and ATlR proteins in homogenized aortic tissue were significantly increased(all P<0.05). ④The plasma AngⅡ level and PAI-1 activity，aortic AngⅡ level and  PAI-1 activity were all closely related to the expressions of p-ERK1/2 and ATlR proteins in homogenized aortic tissue in various groups(r=0.85－0.94,all P<0.01).⑤Compared with AMI group,the AngⅡ levels in plasma and homogenized aortic tissue,and the activity of PAI-1 in plasma and incubation solution for aorta,as well as the expression of p-ERK1/2 and ATlR proteins in the homogenized aortic tissue were markedly reduced(all P<0.05),but the activity of tPA and the ratio of tPA to PAI-1 were enhanced notably in plasma and incubation solution for aorta in PD98059 group(all P<0.05). Conclusion In the condition of AMI,Ang Ⅱcould enhance the synthesis and release of PAI-1 but inhibit the synthesis and release of tPA through activating ATlR to trigger activation of ERK.

Key words: myocardial infarction;extracellular signal-regulated kinase, angiotensin Ⅱ;plasminogen activator inhibitor-1;tissue plasminogen activator;rats,Sprague-Dawley