EFFECTS OF ENALAPRIL ON THE COLLAGEN MATRIX IN CARDIOMYOPATHIC SYRIAN-HAMSTERS (BIG-14.6 AND BIG-53.58)

The hereditary cardiomyopathic strain of Syrian hamster has been exten sively studied as a model of cardiomyopathy and heart failure. We atte mpted to determine whether an angiotensin converting enzyme (ACE) inhi bitor, enalapril, prevents the increase in extracellular collagen matr ix which connects the myocytes in cardiomyopathy. Enalapril was admini stered at an average dosage of 10 mg/kg per day to 10- to 20-week-old hamsters with hypertrophic (Bio 14.6) and dilated (Bio 53.58) cardiomy opathy, as well as to control Syrian hamsters (F1 beta). Collagen conc entration estimated by hydroxyproline concentration and the collagen t ype III:I ratio significantly increased in the hearts of the Bio 14.6 and Bio 53.58 strains at 20 and 40 weeks of age as, compared with thos e in age-matched F1 beta hamsters. When Bio 14.6 hamsters were given e nalapril for 10 weeks from 10 to 20 weeks of age, the collagen concent ration, the collagen type III:I ratio and type III collagen mRNA expre ssion were significantly decreased, compared with those in untreated a nimals of the same strain. After the administration of enalapril, scan ning electron microscopic examination also revealed a decrease in fibr illar collagen accumulation in the interstitium and the network surrou nding the cardiac myocytes. These prophylactic effects were not observ ed in the Bio 53.58 strain. These results indicate that the administra tion of ACE inhibitor prevents type III collagen production in the Bio 14.6 strain but not in the Bio 53.58 strain of Syrian hamster.