THE EFFECTS OF RENIN-ANGIOTENSIN SYSTEM INHIBITION ON AORTIC CHOLESTEROL CONTENT IN CHOLESTEROL-FED RABBITS

To investigate how the renin-angiotensin system (RAS) might be involve d in cholesterol-induced atherosclerosis, we studied the effects of a nonsulhydryl angiotensin converting enzyme (ACE) inhibitor, enalapril, and an angiotensin II receptor antagonist, E-4177, in cholesterol fed rabbits. Japanese white rabbits were randomly divided into four group s with the following dietary regimens: group A (n = 8) received a stan dard diet; group B (n = 8) had a 0.5% cholesterol diet; group C (n = 8 ) had a 0.5% cholesterol diet plus enalapril (10 mg/kg/day, p.o.); gro up D (n = 8) received a 0.5% cholesterol diet plus E-4177 (20 mg/kg/da y, p.o.) and were fed these diets for 5 weeks. Enalapril or E-4177 had no significant effect on either the total plasma or the high density lipoprotein (HDL) cholesterol concentrations. However, the aortic chol esterol content in groups C and D was equally significantly less than that in group B. The plasma and aortic ACE activities were significant ly reduced only in group C compared with those in the other groups. Th e aortic ACE mRNA and AT1 mRNA levels were assessed by a reverse trans cription polymerase chain reaction (RT-PCR). The aortic ACE mRNA level was only significantly less in group C than in any of the other group s. The aortic AT1 mRNA level increased significantly in group B compar ed with that in group A and was significantly and equally reduced in b oth groups C and D compared with that in group B. These data indicate that angiotensin II rather than ACE may therefore be related to aortic cholesterol content. It follows therefore that the inhibition of angi otensin II by either ACE inhibitor or angiotensin II (type 1) receptor antagonist may play a role in prevention of atherosclerosis.