Effects Of Imidapril,Spironolactone And Combination On The 8 Weeks' Ventricular Remodeling And Matrix Metalloproteinases In Acute Myocardial Infarction Rat

Object: Acute myocardial infarction often accompanied with ventricularremodeling and activation of the renin-angiotensin-aldosterone system. Ventricular remodeling includes the changes of cardiac myocytes and extracellular matrix (ECM). The extracellular matrix degradation plays the pivotal roles in the process of ventricular remodeling. Matrix metalloproteinases (MMPs) are a zinc-dependent proteolytic enzymes family, which are responsible for extracellular matrix degradation. Moreover it can be activated after AMI. In present experiment, we investigated the effects of ACEI and spironolactone in single or combined groupd on the vetricular remodeling and MMPs activities in the MI model. Method: 24hours after anterior descending coronary ligation, SD rats were randomized to control group (no therapy, n=l 1), imidapril group (imidapril 2mg/kg/d, n=l 1), spironolactone group (spironolactone 40mg/kg/d, n=9) and combination group (imidapril 2mg/kg/d+ spironolactone 40mg/kg/d, n=10). The rats without operation were put into the sham-operated group. 8 weeks after MI ,echocardiography was performed, plasma Ang II and aldosterone were also determined . MMPs activities were measured by gelatin zymography. Result: 8 weeks after MI, Left and right ventricular relative weights of all operated groups significant increased compared with that of sham-operated rats. Imidapril, spironolactone and their combination can limit its increment compared with the control group. Imidapril and combination group also reduced significantly LVEDD, while spironolactone didn't appear this kind of effect. Before activated by trypsin ,the myocardium expressed MMP-1 activity in all groups . And after activated by trypsin the myocardium also expressed MMP-2, -9 activities. Compared with sham-operated, only MMP-2 upregulated in control group, and imidapril significantly inhibited MMP-2 activity, while spironolactone didn't appear this kind of effect. 8 weeks after MI, plasma Ang II and aldosterone level in control group still increased. Furthermore there was a significantly difference in the mean rank of plasma Ang II and aldosterone in all groups(P<0.05). Ang II riseswere seen in 5 cases (45% )in imidapril group, 3 cases (33%)in spironolactone group, respectively. ALD increments were seen in 4 cases(36%) in imidapril group, 2 cases(22%) in spironolactone group. There was only 1 case (10%) in combination group with AngII rise.Conclusion: 1 .myocardium non-infracted area hypertrophy and left ventricle enlargement occurred at 8 weeks after MI, which can be improved by the treatment of imidapril, spironolactone and their combination. 2. Eight weeks after MI, MMP-2 in a non-activated state upregulated, and imidapril can inhibit its upregulation; spironolatone has no effect on it. 3. Eight weeks after MI, the level of plasma Ang II and aldosterone was still high, which cannot be fully suppressed by the treatment of imidapril, it is inferred that Ang II "reactivation" and aldosterone "escape" occurred. The combination of imidapril and spironolactone can suppress "reactivation" and "escape".