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 pressor 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 approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kowala
M C
MC
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Recce
R
R
Beyer
S
S
Aberg
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G
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D002452:Cell Count / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D006224:Cricetinae; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005487:Foam Cells / Q000187:drug effects; D017328:Fosinopril / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000150:complications* / Q000188:drug therapy; D007091:Image Processing, Computer-Assisted; D008264:Macrophages / Q000187:drug effects; D008297:Male
D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002216:Captopril; D017328:Fosinopril