Cardiovascular Changes by Long-term Inhibition of the Renin-Angiotensin System in Aging

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Abstract
We studied four groups of 20 female mice to evaluate the long-term effect of an angiotensin-converting enzyme on myocardium and vessels during the natural process of aging. Three groups received enalapril in water from weaning to 24 months of age (group A, 20 mg/L; group B, 10 mg/L; group C, 5 mg/L); group D served as a control. Animals surviving after 24 months were killed, and morphometric studies were performed. Total corporal weight was higher in animals receiving enalapril. Cardiac weight relative to total body weight was lower in the treated groups than in the control group. Cardiac morphometric studies showed lower myocardiosclerosis in animals receiving angiotensin-converting enzyme inhibitor (groups A through D, respectively, 0.9±0.6%, 1.1±0.2%, 1.03±0.1%, and 9.5±4.3%; P <.01, groups A, B, and C versus D). The number of mitochondria per myocardiocyte was higher in the groups receiving enalapril (A through D, respectively, 85±7, 85±6, 83±8, and 58±8; P <.01, groups A, B, and C versus D). At the vascular level, vessel diameters were not significantly different between the groups receiving angiotensin-converting enzyme inhibitor and the control group, whereas differences were seen in arterial tunica media thickness (wall-lumen ratio) (groups A through D, respectively, aorta: 0.13±0.02, 0.11±0.02, 0.12±0.01, 2.81±0.35; intrapulmonary: 0.9±0.43, 0.6±0.41, 0.8±0.46, 1.9±0.51; intracerebral: 2.18±0.46, 2.29±0.45, 2.46±0.43, 3.30±0.41; intrarenal: 2.28±0.46, 2.73±0.48, 2.70±0.51, 3.23±0.41; intracariaciac: 2.27±0.44, 2.59±0.41, 2.80±0.43, 3.68±0.47; P <.001, groups A, B, and C versus D). No significant differences in blood pressure were found among the groups. We conclude that cardiovascular changes in aging may be altered by angiotensin-converting enzyme inhibitors.