ONE YEAR STUDY WITH THE ACE INHIBITOR RAMIPRIL IN RATS - PREVENTION OF LEFT-VENTRICULAR HYPERTROPHY WITHOUT BLOOD-PRESSURE REDUCTION

In experimental and clinical studies ACE inhibitors have been demonstrated to be effective in the treatment of cardiac hypertrophy, when used in antihypertensive doses. In order to separate cardiac effects of an ACE inhibitor from those on systemic blood pressure, chronic experiments were performed in rats made hypertensive by aortic banding. For one year rats were treated either with an antihypertensive dose of 1 mg/kg/d ramipril (RA 1 mg) or received a low dose of 10 mug/kg/d ramipril (RA 10 mug) which was non-antihypertensive ( subhypotensive). Chronic treatment with the ACE inhibitor ramipril in the antihypertensive as well as in the subhypotensive dose prevented cardiac hypertrophy and myocardial fibrosis. Plasma ACE activity was reduced in the RA 1 mg but not in the RA 10 mug group. Catecholamines were increased in the stenosis group but treatment with either dose of ramipril approximated the values to that of the sham group. These results in rats with aortic stenosis show that longterm ACE inhibitor treatment with ramipril in antihypertensive and subhypotensive doses prevents cardiac hypertrophy, suggesting cardiovascular benefits beyond blood pressure.