The effect of a putative anti-atherosclerotic agent (S 1204) on lipid metabolism in rabbit aorta.
The effects of the novel fenfluramine derivative, S 1204 (meta-trifluoromethyl phenyl-1 [beta(sulfamyl-3'-chloro-4'-benzoyloxyethyl)]amino-2-propane) were studied on lipid metabolism in rabbit aorta and other tissues. Pretreatment of rabbits with S 1204 (50 mg/kg orally) for 10 days strongly inhibited the aortic incorporation of an intravenous 20 muCi tracer-dose of [4-(14)C]-cholesterol given 24 h earlier. However, incorporation of such cholesterol radioactivity into the liver, intestine, lung or plasma was not affected, in comparison with control animals. One hour after i.v. injection of a 100 muCi tracer-dose of [2-(14)C]acetate, S 1204 significantly reduced the radioactivity of total lipids in the aorta and liver. Such inhibition of acetate incorporation into arterial lipids was observed with all lipid fractions (that is, free fatty acids, esterified cholesterol, especially phospholipids, glycerides and free cholesterol). Incorporation of acetate into intestinal triglyceride fractions was also significantly decreased. The results indicate that S 1204 may have anti-atherogenic properties, which could be valuable in the clinical treatment of atherosclerosis.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D010743:Phospholipids; D014280:Triglycerides; D005277:Fenfluramine; D002784:Cholesterol