Effect of etofibrate on the development and the regression of atheromas in a rabbit model of atherosclerosis.
The study presents the effect of 2-[2-(p-Chlorophenoxy)-2-methylproprionoxy]ethyl nicotinate (Etofibrate, Lipo-Merz) on progression and regression of experimentally induced atheromas. The atheromas (intimal proliferates) were produced in carotid arteries of rabbits fed for 4 weeks a diet containing 1% cholesterol. One carotid artery was stimulated transmurally with weak electrical pulses via chronically implanted electrodes during the 4 weeks in which the animals received the cholesterol-enriched food. The standardized stimulus induced an atheroma in the stimulated region of the artery in all animals. Quantitation was carried out by counting cell layers in serial sections of the stimulated artery region. Lipid accumulation was measured in oil red stained histological sections with a semiquantitative technique. Additionally serum cholesterol, serum triglycerides, and HDL-cholesterol were determined. Addition of 200 mg Etofibrate/kg body weight per day to the cholesterol-enriched food caused a significant inhibition of the proliferation of the smooth muscle cells in the intimal proliferate which consequently resulted in a less pronounced plaque. Stainable lipids were found in all controls and all Etofibrate-treated animals. HDL-cholesterol levels were higher in the treated animals than in the controls while the other lipid parameters were not influenced by Etofibrate. In another set of experiments two groups of rabbits were treated as described above. After the production of an atheroma (4 weeks) they were fed normal food. One of the groups received daily 200 mg Etofibrate/kg body weight, the other not. After the regression period of one year the arteries were excised and sectioned for histology and lipid levels were measured as above.(ABSTRACT TRUNCATED AT 250 WORDS)
Betz
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E
Institute of Physiology (I), University of Tübingen, Federal Republic of Germany.
Quack
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G
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D011817:Rabbits
D000960:Hypolipidemic Agents; C009746:etofibrate; D002995:Clofibric Acid; D002994:Clofibrate