Pravastatin-induced changes in receptor-mediated metabolism of low density lipoprotein in guinea pigs.
The effect of pravastatin, an inhibitor of HMG-CoA reductase, on the metabolism of human low density lipoprotein (LDL) was examined in guinea pigs. Pravastatin treatment significantly reduced plasma levels of total cholesterol and LDL-cholesterol by 15.6 mg/dl (38.8%) and 12.7 mg/dl (42.9%), respectively. We investigated the metabolism of LDL in pravastatin-treated and untreated guinea pigs using the simultaneous intravenous injection of 131I-labeled LDL and 125I-labeled, galactose-treated LDL to quantify the LDL receptor pathway. Pravastatin increased the fractional catabolic rate (FCR) of the LDL receptor-dependent pathway. The treatment with pravastatin did not alter the FCR of the LDL receptor-independent pathway. The FCR of the LDL receptor-dependent pathway was higher for LDL isolated from pravastatin-treated subjects than for LDL isolated from control subjects. These findings suggest that pravastatin mainly reduced plasma cholesterol levels by accelerated FCR of the LDL receptor-mediated pathway.
Matsunaga
A
A
Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Sasaki
J
J
Hidaka
K
K
Takada
Y
Y
Araki
K
K
Moriyama
K
K
Arakawa
K
K
D000818:Animals; D005069:Evaluation Studies as Topic; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D008055:Lipids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D017035:Pravastatin