title: Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids.
abstract: The effect of two angiotensin converting enzyme (ACE) inhibitors on the development of atherosclerosis was determined in hyperlipidemic hamsters. Preliminary studies indicated that only fosinopril (50 mg/kg) temporarily decreased mean arterial pressure, while after chronic dosing fosinopril and captopril (50 mg/kg) were ineffective. The same dose of fosinopril and captopril inhibited the angiotensin I pressor response, indicating these agents suppressed ACE activity in vivo. In the 3 week atherosclerosis experiment, all hamsters were fed chow supplemented with 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with those receiving either 50 mg/kg per day of fosinopril or 50 mg/kg per day of captopril. After 3 weeks, fosinopril reduced plasma total cholesterol, low density lipoprotein (LDL) plus very low density lipoprotein cholesterol and total triglycerides by 17%, 27% and 45%, respectively. Captopril only reduced high density lipoprotein cholesterol by 20%. Neither fosinopril or captopril altered blood pressure at 3 weeks. Atherosclerosis was quantified from en face preparations of the lesion-prone aortic arch that were stained with oil red O (for cholesteryl ester and triglycerides). In control hamsters, oil red O labeled numerous subendothelial macrophage-foam cells located along the inner curvature of the aortic arch. Compared with controls, fosinopril reduced the number of intimal macrophage-foam cells/mm2, foam cell size and the fatty streak area by 85%, 38% and 90%, respectively. Captopril decreased these parameters by 44%, 16% and 53%. Thus captopril decreased early atherosclerosis without affecting plasma LDL cholesterol or blood pressure, which suggested that inhibiting ACE (or kininase II) directly impeded the accumulation and formation of macrophage-foam cells.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ.
authors.forename: M C
authors.initials: MC
authors.lastname: Kowala
authors.forename: R I
authors.initials: RI
authors.lastname: Grove
authors.forename: G
authors.initials: G
authors.lastname: Aberg
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D005487:Foam Cells / Q000473:pathology; D017328:Fosinopril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006949:Hyperlipidemias / Q000150:complications / Q000503:physiopathology*; D008055:Lipids / Q000097:blood*; D008264:Macrophages / Q000473:pathology; D008297:Male
chemical_list: D008055:Lipids; D002784:Cholesterol; D002216:Captopril; D017328:Fosinopril