Effect of simvastatin on receptor mediated metabolism of low density lipoprotein in guinea pigs.
This study examined the effects of simvastatin, an inhibitor of HMG-CoA reductase, on the metabolism of labelled human low density lipoprotein (LDL) in animal models. Administration of 10 mg/kg per day simvastatin for 2 weeks reduced the levels of total cholesterol, LDL-cholesterol and triglycerides by 5.7 mg/dl (16%), 8.8 mg/dl (36%) and 4.9 mg/dl (13%), respectively in guinea pigs. High density lipoprotein-cholesterol levels rose 0.8 mg/dl (29%) by simvastatin treatment. Measurements of turnover of LDL were determined between simvastatin-treated guinea pigs and untreated guinea pigs using intravenous injection of 131I-labelled LDL and 125I-labelled galactose-treated LDL to quantify the LDL receptor pathway. Simvastatin significantly increased the fractional catabolic rate (FCR) of the LDL receptor-dependent pathway. In contrast, the FCR of the LDL receptor-independent pathway was not altered by simvastatin therapy. The FCR for LDL isolated from simvastatin-treated subjects compared to that from control subjects was very similar in both control and simvastatin-fed guinea pigs. These findings suggest that simvastatin mainly reduced serum cholesterol levels by accelerated FCR of LDL receptor mediated pathway.
Matsunaga
A
A
Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Sasaki
J
J
Takada
Y
Y
Hidaka
K
K
Arakawa
K
K
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005690:Galactose; D006168:Guinea Pigs; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D019821:Simvastatin
D000924:Anticholesteremic Agents; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D008148:Lovastatin; D019821:Simvastatin; D005690:Galactose