Converting Enzyme Inhibition Specifically Prevents the Development and Induces Regression of Cardiac Hypertrophy in Rats

Antihypertensive agents have been shown to differ markedly in their effects on the development and regression of cardiac hypertrophy. In view of possible trophic properties of angiotensin II (ANG II), we compared the effects of equipotent antihypertensive doses of the converting enzyme (CE) inhibitor ramipril (1 mg/kg), the calcium antagonist nifedipine (30 mg/kg), and the arterial vasodilator dihydralazine (30 mg/kg) on cardiac mass in rats subjected to banding of the abdominal aorta. Treatment was started either immediately after banding ("prevention experiments") or after hypertension and hypertrophy had already developed ("regression experiments"). Groups of untreated animals with aortic constriction and sham-operated animals served as controls. In the prevention experiments heart weight, myocardial protein content and ANG II plasma levels were significantly increased in untreated animals and in those receiving nifedipine and dihydralazine. In contrast, values obtained in animals treated with ramipril were not different from those seen in normotensive, sham operated controls with the exception of plasma ANG II levels which were lower. Similar results were observed in the second series of studies which examined the effect of antihypertensive agents on the "regression" of cardiac hypertrophy. Treatment was started 6 weeks after aortic banding and continued for another 6 weeks. While all three drugs lowered blood pressure equally well, only ramipril induced a significant and complete regression of cardiac hypertrophy to values not different from sham-operated controls. In addition we studied a group of animals treated with a nonantihypertensive low dose of ramipril (10 micrograms/kg). Remarkably, these animals showed the same complete regression of cardiac hypertrophy as seen in the group receiving the antihypertensive dose of CE inhibitor. Our study indicates a selective advantage of CE inhibitors over other antihypertensive drugs in the prevention and regression of hypertensive cardiac hypertrophy. Importantly, the dissociation between effects on blood pressure and cardiac mass demonstrated in the experiments with a low dose of ramipril stresses the role of factors other than blood pressure and afterload on the development of hypertensive cardiac hypertrophy. One such peptide, thus, may be ANG with its known potential as a growth factor.