EFFECT OF CHLORPROMAZINE ON RAT ARTERIAL LIPID-SYNTHESIS, INVITRO

The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with [14C]acetate and [14C]mevalonate as lipid precursors. Chlorpromazine 0.25 mM in the incubation medium significantly reduced the incorporation of [14C]acetate into free fatty acids (P < 0.01) and total phospholipids (P < 0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from [14C]acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (P < 0.02) and reducing the relative proportion of sphingomyelin (P < 0.001). [14C]Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (P < 0.001) by 0.25 mM chlorpromazine. Studies with [14C]mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35-40% reductions (P < 0.05) in the formation of 14C-labeled squalene and C27 sterols.