| Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate. | |
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MedLine Citation:
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PMID: 6084138 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D M Capuzzi; W H Cevallos |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 6 Suppl 5 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1984 |
Date Detail:
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Created Date: 1985-03-13 Completed Date: 1985-03-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: S847-52 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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