Effect of CS-514 (pravastatin) on VLDL-triglyceride kinetics in rats.
The effect of CS-514 (pravastatin; Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, on triglyceride turnover, was studied in male Wistar rats. CS-514 (15 +/- 1 mg/day per rat) was administered as a 0.04% solution in drinking water for 14 days. Triglyceride and cholesterol in very low density lipoprotein (VLDL) and plasma triglyceride were reduced by treatment with CS-514. Plasma cholesterol level was not suppressed by CS-514. The CS-514 treated rats had a significantly suppressed triglyceride secretion rate (TgSR) during the fed state compared to control rats (0.85 +/- 0.1 vs. 1.07 +/- 0.3 mg/min, P less than 0.05). By contrast, CS-514 treatment did not suppress TgSR after an overnight fast. These data demonstrate that CS-514, an inhibitor of cholesterol biosynthesis can suppress VLDL-triglyceride secretion in rats and that this effect can be modified by dietary manipulation.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D005215:Fasting; D006538:Heptanoic Acids / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D017035:Pravastatin; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism*
D006538:Heptanoic Acids; D008079:Lipoproteins, VLDL; D009281:Naphthalenes; D014280:Triglycerides; D002784:Cholesterol; D017035:Pravastatin