BIOMOLECULAR CHANGES IN THE AGING MYOCARDIUM - THE EFFECT OF ENALAPRIL

Chronic administration of enalapril in the aging mouse prevents myocar dial fibrosis. To investigate the mechanisms involved, we studied 30 C F1 female mice that received enalapril (ENAL:20 mg/L) in their drinkin g water after weaning and 30 control (CONT) mice. Ten animals from eac h group were killed at 12, 18, and 24 months. Half of the samples were prepared for light microscopy (LM) and the other half for electron mi croscopy (EM). Cardiac histologic sections were studied by an image an alyzer (Bioscan OPTIMAS 4.1). We performed the following measurements in cardiomyocytes: mitochondrial number, mitochondrial superoxide dism utase (SOD) using immunohistochemical methods with EM, the percentage of cell cyclin, and apoptosis. The results obtained for CONT and ENAL, respectively were as follows. For cyclin (percentage of positive) our results were: 12 months 17.1 +/- 0.1% and 18.2 +/- 0.8%, 18 months 2. 4 +/- 1.6% (P < .001), and 11.4 +/- 0.1% (P < .001), 24 months 1.2 +/- 1.3% (P < .001), and 8.2 +/- 1.2% (P < .001) with significant differe nces at 18 and 24 months. For the Feulgen method (cell/mm(2)) we found : 12 months CONT 89.7 +/- 1.2, ENAL 84.6 +/- 1.2; 18 months CONT 62.8 +/- 1.2, ENAL 98.7 +/-: 1.3, and 24 months CONT 81.2 +/- 1.3, ENAL 112 .3 +/- 1.4. Apoptosis (percentage of positive) was found to be 12 mont hs 3.7 +/- 0.4% and 1.9 +/- 0.1%, 18 months 7.1 +/- 0.3% (P < .001), a nd 1.5 +/- 0.1% (P < .001), 24 months 10.9 +/- 0.5% (P < .001) and 2.1 +/- 1.8% (P < .001), for CONT and ENAL, respectively; there were sign ificant differences at 18 and 24 months. The number of mitochondria pe r cardiomyocyte were: 12 months 85.9 +/- 1.8 and 87.3 +/- 1.5, 18 mont hs 69.2 +/- 1.5 dagger and 82.2 +/- 1.8 (P < .001), 24 months 54.6 +/- 1.1 (P < .001) and 81.4 +/- 1.6 (P < .001) for CONT and ENAL respecti vely, with significant differences at 18 and 24 months. Mitochondrial SOD was found to be: 12 months 13.6% +/- 0.2% (P < .05) and 17.8% +/-: 1.3% (P < .05), 18 months 7.1% +/- 1.0% (P < .001) and 16.7% +/- 1.6% (P < .001), 24 months 4.1% +/- 0.5% (P < .001), and 12.4% +/- 0.9% (P .001) for CONT and ENAL respectively, with significant differences at 12 months and at 18 and 24 months (ANOVA and contrast Scheffe's test). We conclude that chronic administration of ENAL modifies mitochondria l SOD at 12 months, whereas at 18 and 24 months ENAL was associated wi th higher mitochondrial SOD and a higher mitochondrial number with a g reater cyclin expression, and a lower percentage of apoptosis. Enalapr il may prevent myocardial fibrosis, possibly by causing changes relate d to enzymatic-mitochondrial or cellular cycle modifications. (C) 1998 American Journal of Hypertension, Ltd.