REGRESSION OF EARLY ATHEROSCLEROSIS IN HYPERLIPIDEMIC HAMSTERS INDUCED BY FOSINOPRIL AND CAPTOPRIL

We determined whether inhibiting angiotensin-converting enzyme (ACE) w ith fosinopril or captopril induced the regression of atherosclerosis in hamsters. A presser experiment demonstrated that 100 mg/kg fosinopr il or captopril almost completely inhibited ACE activity in vivo. Anot her study established that feeding hamsters 0.05% cholesterol and 10% coconut oil resulted in rapid and progressive accumulation of oil red O-stained macrophage-foam cells in the aortic arch. In the regression study, three groups of hamsters were fed the same atherogenic diet for 4 weeks to induce fatty lesions in the arch. After 4 weeks, plasma li pids, blood pressure (BP), and atherosclerosis were quantified in cont rol hamsters. Beginning at 4 weeks, the two remaining groups of hamste rs were treated with 100 mg/kg/day fosinopril or 100 mg/kg/ day captop ril for 6 more weeks while receiving the atherogenic diet. After 6-wee k treatment, plasma lipids, BP, and atherosclerosis were quantified in the two treated groups (i.e., study week 10), and they were compared with the 4-week controls. As compared with that in controls, fosinopri l decreased plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterols by similar to 69%. High density lipopr otein (HDL) cholesterol decreased by 16% and total triglycerides decre ased by 56% as compared with that of controls. Captopril did not alter LDL plus VLDL cholesterols or total triglycerides, but HDL cholestero l decreased by 24% as compared with that of the control group. As comp ared with that of control hamsters, mean arterial BP (MAP) decreased b y 9% with captopril treatment, and heart rate (HR) was decreased by bo th fosinopril and captopril. The fosinopril group had 53% fewer macrop hage-foam cells per square millimeter, the foam cells were 32% smaller , there was a 94% reduction in fatty streak area, and 63% less area of extracellular lipid as compared with 4 week controls. Captopril reduc ed foam cell number, size, and fatty streak area by 40, 21, and 56%, r espectively; the area of extracellular lipid particles increased sligh tly. Fosinopril induced the regression of all parameters of early athe rosclerosis, whereas captopril reversed foam cell accumulation and fat ty streak formation.