AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, PERINDOPRIL, PREVENTS PROGRESSION OF PREFORMED ATHEROSCLEROTIC LESIONS IN THE CHOLESTEROL-FED RABBIT

1. The aim was to determine whether the angiotensin converting enzyme inhibitor perindopril, at a concentration approaching that used in human antihypertensive therapy, influences progression of preformed atherosclerotic plaques. 2. Rabbits had their right carotid artery deendothelialized with a balloon catheter, which resulted in the formation of a myointimal thickening. 3. At 14 weeks post surgery groups I, II and III (n=6 per group) were fed a 1% cholesterol-enriched diet for 6 weeks, then group I rabbits were sacrificed. Groups II and III were placed on a normolipidaemic diet for a further 6 weeks with group III rabbits also receiving 0.3 mg day(-1) kg(-1) perindopril. Groups IV and V were treated the same as groups II and III, respectively, except that they received a normal diet throughout. 4. Group I rabbits fed a 1% cholesterol-enriched diet for 6 weeks developed lipid-filled lesions covering 26.3+/-14.3% of the surface area of the descending thoracic aorta, This was exacerbated in rabbits fed a 1% cholesterol diet for 6 weeks followed by 6 weeks on a normal diet (61.2+/-27.3%). In rabbits fed a 1% cholesterol diet for 6 weeks then a normal diet for a further 6 weeks plus 0.3 mg day(-1) kg(-1) perindopril, the percentage surface area covered by lesions was 21.8+/-15.8%. No lesions developed in the aortas of rabbits fed a normal diet. In the right coronary artery the resulting neointima in rabbits fed a 1% cholesterol diet for 6 weeks only was 42.4+/-5.7% of the cross-sectional area of the vessel wall, 57.4+/-8.0% in rabbits receiving 6 weeks' cholesterol diet then 6 weeks' normal diet, 36.0+/-6.6% in rabbits fed a 6-week cholesterol diet then 6 weeks' normal diet with 0.3 mg day(-1) kg(-1) perindopril and 33.2+/-4.9% and 31.8+/-3.1% in rabbits on a normal diet throughout with 0 and 0.3 mg day(-1) kg(-1) perindopril respectively. The cellular composition of the lesions was also altered in perindopril-treated animals, with fewer and smaller fat-filled cells surrounded by more extracellular matrix. 5. Perindopril is effective in preventing progression of existing atherosclerotic lesions in the cholesterol-fed rabbit after 6 weeks on a normal diet.