title: The effect of ACE inhibitors on atheroma formation is potentiated by association with a calcium channel blocker. A biochemical and ultrastructural study.
abstract: The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril maleate and captopril, on the progression of atherosclerosis was investigated. Golden Syrian hamsters were divided into five groups: controls (C), fed a standard chow diet; hypercholesterolemic animals (HH) induced by supplementing the diet with 3% cholesterol and 15% butter; HH treated with enalapril (20 mg/kg/day); HH treated with captopril (60 mg/kg/day) and HH treated simultaneously with enalapril and a calcium channel blocker, diltiazem (45 mg/kg/day). The drugs were administered for one month, concomitantly with the atherogenic diet. As compared to controls, in HH group a significant increase in serum cholesterol (approximately 5 fold) and ACE activity (approximately 3 fold) was found. In HH-treated animals, both drugs maintained the serum ACE activity within the normal values. However, the effect upon serum cholesterol was different: enalapril and its combination with diltiazem had a significant hypocholesterolemic effect (128.8 +/- 25 mg/dl), whereas captopril had no effect on the cholesterol values (326.6 +/- 41.48 mg/dl). Electron microscopical examination of the coronary arteries and aortic valve in all experimental groups indicated a good correlation between the high levels of cholesterol, ACE activity and the development of the atherosclerotic lesions. Captopril treatment inhibits the early phases of atherosclerosis at level of the coronary artery but has no influence upon the lesion development in the aortic valve. By comparison, enalapril and enalapril-diltiazem co-administration impede the development of fatty streaks by decreasing the accumulation of lipids and calcium deposits in the lesion-prone areas examined. These data indicate that: 1) captopril does not have a hypocholesterolemic potential and cannot prevent atheroma formation in heart valves; 2) enalapril, especially combined with diltiazem, has a hypocholesterolemic effect and impedes the development of atheromatous plaque; 3) the anti-atherosclerosis therapy may benefit from the co-administration of an ACE-inhibitor with a calcium antagonist.
authors.affiliation: Institute of Cellular Biology and Pathology, Nicolae Simionescu, Bucharest, Romania.
authors.forename: M
authors.initials: M
authors.lastname: Raicu
authors.forename: L
authors.initials: L
authors.lastname: Pojoga
authors.forename: N
authors.initials: N
authors.lastname: Simionescu
authors.forename: M
authors.initials: M
authors.lastname: Simionescu
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001021:Aortic Valve / Q000473:pathology / Q000648:ultrastructure*; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002216:Captopril / Q000008:administration & dosage; D002784:Cholesterol / Q000097:blood*; D003331:Coronary Vessels / Q000473:pathology / Q000648:ultrastructure*; D006224:Cricetinae; D004036:Diet, Atherogenic; D004110:Diltiazem / Q000008:administration & dosage; D004357:Drug Synergism; D004656:Enalapril / Q000008:administration & dosage; D008297:Male; D008298:Maleates / Q000008:administration & dosage; D008647:Mesocricetus; D008854:Microscopy, Electron
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D008298:Maleates; D004656:Enalapril; C030272:maleic acid; D002784:Cholesterol; D002216:Captopril; D004110:Diltiazem