Abstract
The aim of the present study was to clarify myocardial collagen metabolism in cardiomyopathic hamsters and the effects of the angiotensin converting enzyme inhibitor, captopril, on collagen synthesis.
Cardiac fibroblasts from Bio 14.6 cardiomyopathic hamsters and from non-cardiomyopathic F1b hamsters were cultured and used in the 4th passage. The synthetic activity of collagenous protein from the two types of hamsters was determined by measuring 3H-proline uptake, and the collagen type was subsequently analyzed by SDS-PAGE in cultured cardiac fibroblasts. Also studied were the effects of the angiotensin converting enzyme inhibitor captopril (1μM) on collagen synthesis by cardiac fibroblasts from cardiomyopathic hamsters.
Twenty five-week-old Bio 14.6 hamsters had significantly higher synthetic activity of collagenous protein and rate of collagen synthesis compared with 13-week-old Bio 14.6 hamsters or 25-week-old F1b hamsters [Bio 14.6 (25-week); 12.4±1.6, Bio 14.6 (13-week); 4.8±0.4, F1b (25-week); 8.7±0.9cpm/cell, Bio 14.6 (25-week); 11.0±0.9, Bio 14.6 (13-week); 3.9±0.4, F1b (25-week); 4.8±0.4%, p<0.05]. Qualitatively, 25-week-old Bio 14.6 hamsters had significandy higher synthetic activity of type I, III, IV and V collagens compared with 25-week-old F1b hamsters. The synthetic activity of type III collagen was incrcased the most in the cardiomyopathic group. Captopril (1μM) causcd a significant decrease in synthetic activity of collagenous protein in 25-week-old Bio 14.6 hamsters (12.4±1.6cpm/cell→10.9±1.1cpm/cell, p<0.05). Qualitatively, the synthetic activity of type III collagen was decreased to about half.
Our study revealed enhanced collagen synthetic activity in cardiac fibroblasts from Bio 14.6 hamsters. Captopril improved collagen metabolism in cultured cardiac fibroblasts from Bio 14.6 hamsters not only quantitatively but also qualitatively. The mechanism of this improvement may be related to the cardiac renin angiotensin system.
