THE EFFECT OF ACE-INHIBITORS ON ATHEROMA FORMATION IS POTENTIATED BY ASSOCIATION WITH A CALCIUM-CHANNEL BLOCKER - A BIOCHEMICAL AND ULTRASTRUCTURAL-STUDY

The effect of two angiotensin converting enzyme (ACE) inhibitors, enal april maleate and captopril, on the progression of atherosclerosis was investigated. Golden Syrian hamsters were divided into five groups: c ontrols (C), fed a standard chow diet; hypercholesterolemic animals (H H) induced by supplementing the diet with 3% cholesterol and 15% butte r; HH treated with enalapril (20 mg/kg/day); HH treated with captopril (60 mg/kg/day) and HH treated simultaneously with enalapril and a cal cium channel blocker, diltiazem 145 mg/kg/day). The drugs were adminis tered for one month, concomitantly with the atherogenic diet. As compa red to controls, in HH group a significant increase in serum cholester ol (similar to 5 fold) and ACE activity (similar to 3 fold) was found. In HH-treated animals, both drugs maintained the serum ACE activity w ithin the normal values. However, the effect upon serum cholesterol wa s different: enalapril and its combination with diltiazem had a signif icant hypocholesterolemic effect (128.81+/-25 mg/dl), whereas captopri l had no effect on the cholesterol values (326.6+/-41.48 mg/dl). Elect ron microscopical examination of the coronary arteries and aortic valv e in all experimental groups indicated a good correlation between the high levels of cholesterol, ACE activity and the development of the at herosclerotic lesions. Captopril treatment inhibits the early phases o f atherosclerosis at the level of the coronary artery but has no influ ence upon the lesion development in the aortic valve. By comparison, e nalapril and enalapril-diltiazem co-administration impede the developm ent of fatty streaks by decreasing the accumulation of lipids and calc ium deposits in the lesion-prone areas examined. These data indicate t hat: 1) captopril does not have a hypocholesterolemic potential and ca nnot prevent atheroma formation in heart valves; 2) enalapril, especia lly combined with diltiazem, has a hypocholesterolemic effect and impe des the development of atheromatous plaque; 3) the anti-atherosclerosi s therapy may benefit from the co-administration of an ACE-inhibitor w ith a calcium antagonist.