EFFECTS OF SIMVASTATIN ON PLASMA-LIPOPROTEIN CONCENTRATIONS AND VERY-LOW-DENSITY LIPOPROTEIN SECRETION IN THE RAT

The effects of simvastatin, a cholesterol biosynthesis inhibitor, on p lasma lipoprotein concentrations and very-low-density lipoprotein (VLD L) secretion were investigated in the rat. The results showed that sim vastatin did not significantly modify plasma lipid levels but did incr ease the cholesterol level of apolipoprotein E-rich high-density lipop roteins (+31%). The treatment significantly reduced total VLDL secreti on (-26%), assessed by VLDL-triacylglycerol accumulation in plasma aft er lipolysis inhibition by Triton WR 1379. Since intestinal VLDL produ ction, which was measured in rats fed erotic acid in order to block th e hepatic secretion of lipoproteins, was not changed, we deduced that simvastatin reduced by 50% the hepatic VLDL secretion. Furthermore, wh ole-body cholesterol production, assessed by the sterol balance, appea red inhibited in the rat after long-term simvastatin treatment.