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

We determined whether inhibiting angiotensin-converting enzyme (ACE) with fosinopril or captopril induced the regression of atherosclerosis in hamsters. A presser experiment demonstrated that 100 mg/kg fosinopril or captopril almost completely inhibited ACE activity in vivo. Another 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 lipids, blood pressure (BP), and atherosclerosis were quantified in control hamsters. Beginning at 4 weeks, the two remaining groups of hamsters were treated with 100 mg/kg/day fosinopril or 100 mg/kg/ day captopril for 6 more weeks while receiving the atherogenic diet. After 6-week 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, fosinopril decreased plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterols by similar to 69%. High density lipoprotein (HDL) cholesterol decreased by 16% and total triglycerides decreased by 56% as compared with that of controls. Captopril did not alter LDL plus VLDL cholesterols or total triglycerides, but HDL cholesterol decreased by 24% as compared with that of the control group. As compared with that of control hamsters, mean arterial BP (MAP) decreased by 9% with captopril treatment, and heart rate (HR) was decreased by both fosinopril and captopril. The fosinopril group had 53% fewer macrophage-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 reduced foam cell number, size, and fatty streak area by 40, 21, and 56%, respectively; the area of extracellular lipid particles increased slightly. Fosinopril induced the regression of all parameters of early atherosclerosis, whereas captopril reversed foam cell accumulation and fatty streak formation.