EFFECT OF CAPTOPRIL ON THE PREVENTION AND REGRESSION OF MYOCARDIAL-CELL HYPERTROPHY AND INTERSTITIAL FIBROSIS IN PRESSURE OVERLOAD CARDIAC-HYPERTROPHY

This article reports on the effects of captopril on both the prevention and the regression of myocardial cell hypertrophy and interstitial fibrosis in experimental animals (rats) with pressure overloaded hearts. Constriction of the abdominal aorta just below the diaphragm during periods of 20 days (prevention experiment) and 40 days (regression experiment) resulted in hypertension and cardiac hypertrophy. In the prevention experiment, captopril was able to inhibit the development of high blood pressure levels and cardiac hypertrophy in aortic-constricted rats. Similarly, the treatment of sham-operated rats with captopril led to a reduction in the weight of the heart and in the myocyte diameter compared with controls. The myocyte volume fraction of the left ventricles of both aortic-constricted and sham-operated animals that were treated with captopril was significantly diminished compared with that of the control group. The interstitial collagen volume fraction of all experimental groups was elevated as compared with the control group. As a consequence, the ratios of myocytes to interstitial collagen in groups of aortic-constricted rats, aortic-constricted rats that were treated with captopril, and sham-operated rats that were treated with captopril were reduced compared with the control group; that is, although captopril was able to prevent myocardial cell hypertrophy after aortic constriction, it could not prevent the maintenance of a normal ratio of myocytes to interstitial collagen, which was due to increased collagen volume fraction. In the regression experiment, captopril lowered high blood pressure levels and augmented heart weights to control values. The mean myocyte transverse diameter in aortic-constricted rats that were treated with captopril was significantly smaller than that of controls. Besides, sham-operated rats that were treated with captopril showed reduced myocyte diameter compared with controls, although their heart weights were not statistically different from control values. The morphometric study demonstrated that only the interstitial collagen volume fraction of the left ventricles of aortic-constricted rats differed from controls. As expected, the ratio of myocytes to interstitial collagen differed from control values only in this group; that is, aortic-constricted rats that were treated with captopril showed regression in myocardial cell hypertrophy that was associated with a decrease in interstitial collagen volume fraction and maintenance of a normal ratio of myocytes to interstitial collagen. These results, besides giving support to the hypothesis that growth of cellular constituents of the myocardial parenchyma and stroma seem to have different regulatory mechanisms, suggest that hypertrophy and regression of hypertrophy are different biologic phenomena.