Expression Of Angiotensin-Converting Enzyme 2 After Myocardial Ischemic Reperfusion Injury And The Effect Of Preconditioning With Losartan

Objective To observe the expression of ACE2 protein,Angâ…¡after myocardial ischemic reperfusion injury(MIRI) in rats, and to study the relationship between angiotensin-converting enzyme2 (ACE2) protein, angiotensinâ…¡(Angâ…¡) expression and myocardial ischemical changes. We evaluate the value of ACE2 protein in the part of MIR and to approach or consummate the mechanism of MIRI. We are ready to study the relationship between arrhythmias induced by reperfusion in intactcanine and the QT interval, ACE2.METHODS Sixty male Sprague Dawley (SD) rats were subjected to coronary artery (LAD) ligation as ischemia/reperfusion heart model and were randomly divided into six groups of ten rats each. The ischemia time was 30minutes. The rat hearts were excised at 0, 1, 3, 6, 9, 12 hours after reperfusion. Angiotensinâ…¡in abdominal aorta blood and myocardial tissues were observed. The myocardium, kidney, testis, Liver were examined immunohistochemically to localize ACE2. Meanwhile, by the way of testing electrocardiogram(ECG), we are able to observe the arrhythmia and the change of S-T segment .RESULTS Except at the time of 12 hours after reperfusion,almost expression of ACE2 wasn't found in no-ischemic and ischemic myocardial tissues. However,ACE2 protein expression was first observe mainly in renal tubular epithelial cells and testis tissues on 1 hour after myocardial ischemic reperfusion (MIRI1h) group. Compared with that of rats on other groups, ACE2 protein expression in kidneys increased significantly. Compared with sham groups, the level of Angâ…¡in ischemic myocardium and artery blood has striking distinction.But the level of Angâ…¡in non-ischemic myocardium has no distinction.CONCLUSION Ischemia and hypoxia may promote or elevate the expression of ACE2 protein. At the time of 720 minutes after reperfusion, expression of ACE2 in rat hearts was upragulated, which might be associated with delayed reperfusion injury. Hypoxia and ischemia couldn't result in the expression of ACE2 protein in ischemic myocardium as well as in non-ischemic area at once. But it can markedly increase the expression of ACE2 in remote organ kidney, especially at the time of 1 hour after reperfusion. The ACE2 protein was the important substance which possibly protected the ischemic myocardium as well as attended the remote organ effect. At the same time, MIR is able to induce the incidence rate of arrhythmia and increase changes of S-T segment in ECG. The correlation coefficient is positive among the level of ACE2 protein and QT interval. Objective To study the relationship between angiotensin-converting enzyme2 (ACE2) protein,angiotensin-â…¡(Angâ…¡)expression and myocardial ischemical changes,and to observe the effects of losartan (Los) pharmacological preconditioning (PPC) on ACE2 protein,Angâ…¡expression of the myocardial ischemic reperfusion injury(MIRI) in rats. We also measured ACE2 protein,Angâ…¡and to evaluate the value of ACE2 protein in the part of MIR treated with Losartan and to approach or consummate the mechanism of MIR.METHODS Sixty Sprague Dawley (SD) rats were randomly divided into 5 groups of twelve rats each: ischemia group (Sham), 1 hour reperfusion group(MIRI1h); and 1 hour reperfusion group treated with losartan group(Los1h), 12 hours reperfusion group (MIRI12h); and 12 hours reperfusion group treated with losartan group(Los12h). Heart,Kidney,Liver,testis activity and angiotensin-â…¡in artery blood and myocardial tissues were observed. The myocardial and renal,Liver,testis cellular expression of ACE2 protein in different reperfusion phases and effects of losartan on MIR were observed by immunohistochemical staining. Meanwhile, by the way of testing electrocardiogram (ECG), we are able to observe the arrhythmia and the change of ST segment of rats. RESULTS Except 12 hours reperfusion,almost no ACE2 protein expression was found in no-ischemic and ischemic myocardial tissues. However,ACE2 protein expression was first observe mainly in renal tubular epithelial cells and testis tissues 60minutes reperfusion. Compared with that of rats with Sham, ACE2 protein expression in kidneys of MIRI rats treated with Losartan increased significantly. Serum levels of Angâ…¡in some groups has striking distinction, myocardial tissues levels of Angâ…¡in some groups has no striking distinction. These results provide evidence for an effect of Angiotensinâ…¡receptor blocker (ARB) on cardiac ACE2 that may be due to direct blockade of AT1R or a modulatory effect of increased angiotensin-(1-7).CONCLUSION In the late-stage of reperfusion, the expression of ACE2 in rat hearts subjected to ischemia followed by reperfusion (P<0.05) was increased. Hypoxia and ischemia couldn't result in the expression of ACE2 in ischemic myocardium as well as in non-ischemic area at once. But it can markedly increase the expression of ACE2 in remote organ kidney, especially treated with Losartan. And losartan pharmacological preconditioning could significantly promote or elevate the expression of ACE2 protein in ischemia myocardium and kidney. The ACE2 protein was the important substance which possibly protected the ischemic myocardium as well as attended the remote organ effect. At the same time, Losartan is able to cut down the incidence rate of arrhythmia and decrease changes of ST segment. Losartan could prolong the QT interval and refrain the change of ST segment under the condition of repeifusion, thus to suppress the repeifusion arrhythmias.