Losartan Pretreatment Inhibits an Early Activation of Matrix Metalloproteinases in Acute Myocardial Infarction

To elucidate the role of matrix metalloproteinase in acute myocardial infarction (MI), we examined collagen degradation by zymography (collagenolytic and gelatinolytic activities). MI was found to be induced by a surgical occlusion of the left coronary artery in the rat, and then the findings were compared with those in sham-operated rats, as a control specimens. Experimental samples were taken from infarcted tissue specimens of the left ventricle (LV) after occlusion. The collagenolytic activities were assessed by zymography and denatured 3H-collagen type I. Zymography showed a significant amount of MMP-1 (interstitial collagenase), MMP-2 (gelatinase) and MMP-9 (neutrophil gelatinase) in the infarcted lesion from 6 to 48 hours after a coronary artery ligation. Myeloperoxidase activity significantly increased in infarcted lesions at 24 hours after the induction of MI. The collagenolytic activity determined by denatured 3H-collagen type I also increased in the infarcted lesion 24 hours after MI. The pretreatment with losartan (20mg/kg) significantly decreased the collagen concentration and inhibited both the MMP-2 and MMP-9 activities. Losartan thus appears to have a beneficial effect on the infarcted myocardium in the early remodeling process after MI by preventing the formation of angiotensin II.