Effects of Pravastatin Sodium Alone and in Combination with Cholestyramine on Hepatic, Intestinal and Adrenal Low Density Lipoprotein Receptors in Homozygous Watanabe Heritable Hyperlipidemic Rabbits

The Japanese Journal of Pharmacology

Hiroshige Itakura¹  Masaharu Fukami⁴  Takashi Ito³  Akiyo Matsumoto¹  Yoshio Watanabe³  Futoshi Nara²  Masao Kuroda²  Junichiro Fukushige⁴  Masashi Shiomi³  Yoshio Tsujita² 

[1] The National Institute of Health and Nutrition;Fermentation Research Laboratories Sankyo Co., Ltd.;Institute of Experimental Animals, Kobe University School of Medicine;Biological Research Laboratories Sankyo Co., Ltd.

关键词: WHHL rabbits;    LDL receptor;    Pravastatin;    HMG-CoA reductase inhibitor;    Cholestyramine;   

DOI  :  10.1254/jjp.59.65

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(32)Cited-By(9)Pravastatin sodium (pravastatin), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was administered alone (50 mg/kg) or in combination with cholestyramine, a bile acid sequestrant resin, at the level of 2% in the diet to homozygous Watanabe heritable hyper-lipidemic (WHHL) rabbits for 4 weeks. The low density lipoprotein (LDL)-cholesterol levels were reduced by 29% and 56% with pravastatin alone and the combination treatment, respectively. Hepatic LDL receptor activity was increased by 11.2- and 13.9-fold with pravastatin alone and the combination treatment, respectively. The LDL receptor activity in the untreated homozygous WHHL rabbits was only 2.5% of that in the normal rabbits. mRNA for the LDL receptor in the liver was also increased by 2.1- and 3.4-fold with pravastatin alone and the combination treatment, respectively. On the other hand, mRNA for the LDL receptor in the adrenal gland was not affected by pravastatin and the combination treatment, whereas the mRNA in the intestine was increased in both groups. These results suggest the following: 1) the induction of hepatic LDL receptor activity by the treatment of pravastatin alone or in combination with cholestyramine is the main cause of the reduction of serum cholesterol levels by these treatments even in LDL receptor-deficient animals. 2) The induction of the mRNA for the LDL receptor in the liver and intestine, but not that in the adrenal gland, might be a reflection of the tissue-selective inhibition of cholesterol synthesis by pravastatin.

【 授权许可】

Unknown