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.