Document Detail

Effect of verapamil and nifedipine on cholesteryl ester metabolism and low-density lipoprotein oxidation in macrophages.
MedLine Citation:
PMID:  7857326     Owner:  NLM     Status:  MEDLINE    
Using mouse macrophage cultures, the effects of verapamil and nifedipine on cholesteryl ester and low-density lipoprotein (LDL) metabolism were studied with special reference to the following parameters: (a) incorporation of [14C]oleate into cholesteryl esters (ChE), (b) contents of total and free cholesterol (FCh), (c) liberation of [14C]oleate from ChE and incorporation of [3H]FCh into ChE, (d) excretion of [3H]Ch from the cells, and (e) LDL oxidation. Verapamil and nifedipine (10-100 microM) were shown to decrease in a dose-dependent manner the incorporation of [14C]oleate into ChE and to increase the concentration of FCh but had no appreciable effect on the concentration of total cholesterol in macrophages cultured in the presence of acetylated LDL. The drugs stimulated the liberation of [14C]oleate from cellular ChE. The pharmacological concentrations (25-75 microM) of verapamil and nifedipine increased the excretion of [3H]FCh from ChE of macrophages in the presence of serum and high-density lipoproteins. The same concentrations of the drugs inhibited both LDL-derived malonyldialdehyde-like products and nitroblue tetrazolium dye reduction in a dose-dependent fashion. The results obtained suggest that verapamil and nifedipine exert their macrophage-mediated antiatherosclerotic effect via reduction of LDL oxidative modification, reduction of intracellular ChE synthesis, stimulation of ChE hydrolysis and cholesterol excretion from the cells.
M I Dushkin; Y S Schwartz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  49     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-03-14     Completed Date:  1995-03-14     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  389-97     Citation Subset:  IM    
Department of Atherogenesis, Siberian Branch of Russian Academy of Medical Science, Novosibirsk.
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MeSH Terms
Cells, Cultured
Cholesterol / analysis
Cholesterol Esters / metabolism*
Esterification / drug effects
Lipoproteins, LDL / metabolism*
Macrophages / drug effects*,  metabolism
Nifedipine / pharmacology*
Oleic Acid
Oleic Acids / metabolism
Oxidation-Reduction / drug effects
Tetrazolium Salts
Verapamil / pharmacology*
Reg. No./Substance:
0/Cholesterol Esters; 0/Lipoproteins, LDL; 0/Oleic Acids; 0/Tetrazolium Salts; 112-80-1/Oleic Acid; 1871-22-3/4-anisyltetrazolium blue; 21829-25-4/Nifedipine; 52-53-9/Verapamil; 57-88-5/Cholesterol

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