Document Detail

Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid.
MedLine Citation:
PMID:  8447448     Owner:  NLM     Status:  MEDLINE    
Metabolites of arachidonic acid regulate several physiological processes, including vascular tone. The purpose of this study was to determine which metabolites of arachidonic acid are produced by bovine coronary arteries and which may regulate coronary vascular tone. Arachidonic acid induced a concentration-related, endothelium-dependent relaxation [one-half maximum effective concentration (EC50) of 2 x 10(-7) M and a maximal relaxation of 91 +/- 2% at 10(-5) M] of bovine coronary arteries that were contracted with U-46619, a thromboxane mimetic. The concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of prostaglandin I2 (PGI2), increased from 82 +/- 6 to 328 +/- 24 pg/ml with arachidonic acid (10(-5) M). Treatment with the cyclooxygenase inhibitor indomethacin attenuated arachidonic acid-induced relaxations by approximately 50% and blocked the synthesis of 6-keto-PGF1 alpha. PGI2 caused a concentration-related relaxation (EC50 of 10(-8) M and a maximal relaxation of 125 +/- 11% at 10(-7) M). BW755C, a cyclooxygenase and lipoxygenase inhibitor, inhibited arachidonic acid-induced relaxation to the same extent as indomethacin. When vessels were treated with both indomethacin and BW755C, the inhibition of relaxation was the same as either inhibitor alone. SKF 525a, a cytochrome P-450 inhibitor, reduced arachidonic acid-induced relaxation by approximately 50%. When SKF 525a was given in combination with indomethacin, the relaxation by arachidonic acid was almost completely inhibited. SKF 525a inhibited the synthesis of epoxyeicosatrienoic acids (EETs).(ABSTRACT TRUNCATED AT 250 WORDS)
M Rosolowsky; W B Campbell
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  264     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-04-06     Completed Date:  1993-04-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H327-35     Citation Subset:  IM    
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
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MeSH Terms
8,11,14-Eicosatrienoic Acid / analogs & derivatives*,  pharmacology
Arachidonic Acid / pharmacology*
Arteries / drug effects
Coronary Vessels / drug effects*
Epoprostenol / physiology*
Grant Support
Reg. No./Substance:
35121-78-9/Epoprostenol; 506-32-1/Arachidonic Acid; 7324-41-6/8,11,14-Eicosatrienoic Acid; 81246-84-6/5,6-epoxy-8,11,14-eicosatrienoic acid; 81276-02-0/11,12-epoxy-5,8,14-eicosatrienoic acid; 81276-03-1/14,15-epoxy-5,8,11-eicosatrienoic acid

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