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.