Effect of perindopril on the development of atherosclerosis in the cholesterol-fed rabbit.
1. The aim of the study was to examine the effect of the angiotensin-converting enzyme inhibitor perindopril on the development of atheroma in the cholesterol-fed rabbit. 2. The normal human carotid artery, like most large human arteries, has a preformed diffuse intimal thickening. To model this thickening, the right carotid artery of the 12-week-old rabbit had an expanded balloon catheter passed down it to remove the endothelium and partially damage the media. 3. Fourteen weeks after this operation, a myointimal thickening similar in almost all respects to the human intimal thickening had developed. The rabbits were then divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a 1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); (iii) a 1% cholesterol diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day). 4. After 6 weeks of treatment the animals were sacrificed. There were ameliorating effects of both hypotensive and non-hypotensive doses of perindopril on the development of plaques, as determined by the area of intima covered by Oil Red-O-staining plaque and light microscopy. 5. Cell culture studies indicated that perindopril has no effect on smooth muscle proliferation, but increases collagen and non-collagen synthesis by smooth muscle cells and decreases their binding of the atherogenic lipoprotein beta-very low density lipoprotein (beta-VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
J H
JH
Department of Anatomical Sciences, University of Queensland, Brisbane, Australia.
Fennessy
P
P
Campbell
G R
GR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003094:Collagen / Q000096:biosynthesis; D007211:Indoles / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020913:Perindopril; D011485:Protein Binding; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D007211:Indoles; D008079:Lipoproteins, VLDL; D003094:Collagen; D020913:Perindopril