Pravastatin sodium, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreases serum total cholesterol in Japanese White rabbits by two different mechanisms. 2002

Atsuhiro Miyazaki, and Teiichiro Koga
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., Hiromachi 1-2-58, Shinagawa-ku, 140-8710, Tokyo, Japan.

Pravastatin sodium (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), when orally administered to male Japanese White (JW) rabbits at 1-30 mg/kg for 21 days, decreased the concentrations of total cholesterol, low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol in a dose-dependent manner. On the other hand, pravastatin did not change the concentration of serum triglycerides and very low density lipoprotein (VLDL)-cholesterol. On day 21, LDL-cholesterol was significantly decreased at doses higher than 3 mg/kg, whereas HDL-cholesterol was significantly reduced at doses higher than 10 mg/kg. The concentrations of hepatic LDL receptor proteins determined by immunoblot analysis increased at the same dose at which the concentrations of LDL-cholesterol decreased. The serum concentrations of HDL-cholesterol were decreased at the same dose at which VLDL-cholesterol secretion rates from the liver were reduced. The present study suggests that in JW rabbits, pravastatin decreases the serum concentration of LDL-cholesterol through an LDL receptor pathway, whereas the agent lowers the concentration of HDL-cholesterol by the mechanisms associated with a reduction of VLDL-cholesterol secretion from the liver.

UI MeSH Term Description Entries
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008079 Lipoproteins, VLDL A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues. Pre-beta-Lipoprotein,Prebeta-Lipoprotein,Prebeta-Lipoproteins,Very Low Density Lipoprotein,Very-Low-Density Lipoprotein,Very-Low-Density Lipoproteins,Lipoprotein VLDL II,Lipoproteins, VLDL I,Lipoproteins, VLDL III,Lipoproteins, VLDL1,Lipoproteins, VLDL2,Lipoproteins, VLDL3,Pre-beta-Lipoproteins,Lipoprotein, Very-Low-Density,Lipoproteins, Very-Low-Density,Pre beta Lipoprotein,Pre beta Lipoproteins,Prebeta Lipoprotein,Prebeta Lipoproteins,VLDL Lipoproteins,VLDL1 Lipoproteins,VLDL2 Lipoproteins,VLDL3 Lipoproteins,Very Low Density Lipoproteins
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D002785 Sterol O-Acyltransferase An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26. Acyl-CoA-Cholesterol Acyltransferase,Cholesterol Acyltransferase,Cholesterol Esterifying Enzyme,Acyl CoA Cholesterol Acyltransferase,Acyltransferase, Acyl-CoA-Cholesterol,Acyltransferase, Cholesterol,Enzyme, Cholesterol Esterifying,Esterifying Enzyme, Cholesterol,O-Acyltransferase, Sterol,Sterol O Acyltransferase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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