DIFFERENTIAL-EFFECTS OF RENIN-ANGIOTENSIN SYSTEM BLOCKADE ON ATHEROGENESIS IN CHOLESTEROL-FED RABBITS

To investigate the mechanism by which angiotensin-converting enzyme (A CE) inhibition attenuates atherogenesis, we have studied the effects o f a nonsulfhydryl ACE inhibitor, enalapril, and an angiotensin recepto r antagonist, SC-51316, in cholesterol-fed rabbits. After 3 mo of enal april treatment (10 mg/kg per d, p.o.) the percent plaque areas in the thoracic aortas of treated animals were significantly reduced (contro ls: 86.8+/-3.5%; treated: 31.1+/-8%, P < 0.001 ). Aortic cholesterol c ontent was also reduced (controls: 31.4+/-3.2 mg/g tissue; treated: 7. 4+/-1.8 mg/g, P < 0.001 ). Enalapril had no significant effect on plas ma lipid levels or conscious blood pressure. In a second study, the an giotensin II receptor antagonist SC-51316 was administered at a dose e quivalent to enalapril at blocking angiotensin pressor effects in vivo (30 mg/kg per d, p.o.). Evaluation after 3 mo indicated no significan t attenuation of aortic atherosclerosis. These results demonstrate tha t: (a) enalapril attenuates atherogenesis without affecting either blo od pressure or plasma lipid levels; (b) antioxidant activity, found wi th sulfhydryl-containing ACE inhibitors, is not necessary for reducing plaque formation; and (c) the attenuation of atherogenesis by ACE inh ibition may not be due to blockade of the renin-angiotensin system. Al ternatively, one must consider the multiple effects of ACE inhibition on other hormone systems, such as bradykinin, or the possibility that alternate angiotensin II receptors may be involved in atherosclerosis.