Document Detail

Possible inhibitory function of endogenous 15-hydroperoxyeicosatetraenoic acid on prostacyclin formation in bovine aortic endothelial cells.
MedLine Citation:
PMID:  3081039     Owner:  NLM     Status:  MEDLINE    
Arachidonic acid is metabolized via the cyclooxygenase pathway to several potent compounds that regulate important physiological functions in the cardiovascular system. The proaggregatory and vasoconstrictive thromboxane A2 produced by platelets is opposed in vivo by the antiaggregatory and vasodilating activity of prostacyclin (prostaglandin I2) synthesized by blood vessels. Furthermore, arachidonic acid is metabolized by lipoxygenase enzymes to different isomeric hydroxyeicosatetraenoic acids (HETE's). This metabolic pathway of arachidonic acid was studied in detail in endothelial cells obtained from bovine aortae. It was found that this tissue produced 6-ketoprostaglandin F1 alpha as a major cyclooxygenase metabolite of arachidonic acid, whereas prostaglandins F2 alpha and E2 were synthesized only in small amounts. The monohydroxy fatty acids formed were identified as 15-HETE, 5-HETE, 11-HETE and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT). The latter two compounds were produced by cyclooxygenase activity. Nordihydroguaiaretic acid (NDGA), a rather selective lipoxygenase inhibitor and antioxidant blocked the synthesis of 15- and 5-HETE. It also strongly stimulated the cyclooxygenase pathway, and particularly the formation of prostacyclin. This could indicate that NDGA might exert its effect on prostacyclin levels by preventing the synthesis of 15-hydroperoxyeicosatetraenoic acid (15-HPETE), a potent inhibitor of prostacyclin synthetase. 15-HPETE could therefore act as an endogenous inhibitor of prostacyclin production in the vessel wall.
B Mayer; R Moser; H Gleispach; W R Kukovetz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  875     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1986 Feb 
Date Detail:
Created Date:  1986-04-02     Completed Date:  1986-04-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  641-53     Citation Subset:  IM    
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MeSH Terms
Aorta, Thoracic / metabolism
Arachidonic Acid
Arachidonic Acids / metabolism,  physiology*
Blood Vessels / metabolism*
Catechols / pharmacology
Endothelium / metabolism
Epoprostenol / biosynthesis*
Fatty Acids / metabolism
Gas Chromatography-Mass Spectrometry
Lipid Peroxides / physiology*
Nordihydroguaiaretic Acid
Reg. No./Substance:
0/Arachidonic Acids; 0/Catechols; 0/Fatty Acids; 0/Leukotrienes; 0/Lipid Peroxides; 35121-78-9/Epoprostenol; 500-38-9/Nordihydroguaiaretic Acid; 506-32-1/Arachidonic Acid; 67675-14-3/15-hydroperoxy-5,8,11,13-eicosatetraenoic acid

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

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