Effect of etofibrate and its metabolites on atheromas of rabbits and on smooth muscle cell cultures.
In rabbits electrodes were implanted on either side of a carotid artery wall in a way such that transmural electrical stimulation could be performed on the unrestrained animal. Daily repetition of stimulation (100 microA, 10 Hz, 10 ms/imp), 30 min in the morning and 15 min in the afternoon, causes a fibromuscular intimal proliferate below the anode. With additional feeding of a cholesterol-rich diet the proliferate develops into a typical atheroma. The use of defined intensity of the stimuli and a constant period of stimulation (4 weeks) allows a standardization of the plaque development and thus the study of the effects of growth promoting or growth suppressing drugs. The in vivo experiments were supplemented with a study of the effects of the same drugs on the growth of vascular smooth muscle cells and fibroblasts in cell cultures. This combination of experiments increased the value of either results given that the drugs show similar effects in both types of experiments. 2-[2-(p-Chlorophenoxy)-2-methylpropionoxy]ethyl nicotinate (etofibrate, Lipo-Merz) was seen to inhibit the growth of atheromas to a certain degree in vivo. A dose dependent suppression of the rate of mitoses of vascular smooth muscle cells (SMC) and of fibroblasts was observed in vitro. Etofibrate caused a slight decrease in the serum cholesterol and a significant increase in serum high density lipoproteins in the animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology*; D001011:Aorta; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002999:Clone Cells; D004558:Electric Stimulation; D005347:Fibroblasts / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D008075:Lipoproteins, HDL; D014280:Triglycerides; C009746:etofibrate; C048164:etofibrate 2-hydroxymethyl-2-(4-chlorophenoxy)-2-methyl propionate; C048163:etofibrate 2-hydroxymethylnicotinate; D002995:Clofibric Acid; D002784:Cholesterol; D002994:Clofibrate