Document Detail


Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate.
MedLine Citation:
PMID:  6084138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abundant evidence exists for the cumulative adverse effects of hypertension and hypercholesterolemia on the progression of coronary heart disease. The antihypertensive drug guanabenz acetate has been shown to lower serum cholesterol levels, but the mechanism for this effect is unclear. To explore this problem, suspensions of rat liver cells were incubated with guanabenz and labeled lipogenic precursors. Guanabenz produced an inhibition of cholesterol production from [14C]acetate that ranged from 10% at 0.005 mM guanabenz to 90% at 0.20 mM guanabenz. Inhibition of cholesterol production from [14C]mevalonate was half as great as inhibition from [14C]acetate. Thus, guanabenz inhibits hepatic cholesterol production at both pre- and postmevalonic sites in the sterol pathway. Synthesis of triglycerides from [14C]palmitate also was inhibited by guanabenz, whereas oxidation of [14C]palmitate to 14CO2 was stimulated. Therefore, the inhibition of triglyceride formation from fatty acid produced by guanabenz may be due to the stimulation of fatty acid oxidation. The clinical effects of guanabenz on serum lipid levels may relate to its direct actions on hepatic cholesterol and triglyceride biosynthesis.
Authors:
D M Capuzzi; W H Cevallos
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  6 Suppl 5     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1984  
Date Detail:
Created Date:  1985-03-13     Completed Date:  1985-03-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S847-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carbon Dioxide / metabolism
Cholesterol / biosynthesis*
Depression, Chemical
Guanabenz / pharmacology*
Guanidines / pharmacology*
Liver / metabolism*
Male
Mevalonic Acid / metabolism
Oxidation-Reduction
Palmitic Acid
Palmitic Acids / metabolism
Proteins / metabolism
Rats
Rats, Inbred Strains
Triglycerides / biosynthesis*
Chemical
Reg. No./Substance:
0/Guanidines; 0/Palmitic Acids; 0/Proteins; 0/Triglycerides; 124-38-9/Carbon Dioxide; 150-97-0/Mevalonic Acid; 5051-62-7/Guanabenz; 57-10-3/Palmitic Acid; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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