Document Detail


Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate.
MedLine Citation:
PMID:  968049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Isolated bovine, canine, and human coronary arteries exhibited dose dependent contractions to prostaglandin (PG) E2 and F2alpha (50 ng/ml to 10mug/ml). The ED50 value for both PGE2 and PGF2alpha was 500 ng/ml in the bovine and human coronary arteries. Paradoxically, although PGE2 and gf2alpha are vasoconstrictors, administration of their precursor, arachidonate (100 ng/ml to 10 mug/ml) caused relaxation of the bovine, canine and human coronary arteries. This observation suggests that arachidonate is not being converted by the coronary PG synthetase to PGE2 or PGF2alpha. However, the arachidonate induced coronary relaxation was inhibited by pretreatment with PG synthetase inhibitors, indomethacin, meclofenemate and aspirin. Indomethacin addition to the strips previously relaxed by arachidonate caused contraction. In contrast to other PGs (E2 and F2alpha), PGE1 (10 ng/ml to 10 mug/ml) caused dose dependent relaxation of the bovine coronary arteries (ED50 = 100 ng/ml). Indomethacin induced further relaxation of the blood vessels previously relaxed by PGE1. Since PGE1 cannot arise from arachidonate, the arachidonate coronary dilation and reversal by indomethacin must be independent of PGE1 formation. Linolenate (100 ng/ml to 10 mug/ml) and oleate (100 ng/ml to 10 mug/ml) also caused relaxation of the bovine coronary blood vessels both before and after indomethacin, thereby eliminating a direct non-specific fatty acid effect as the cause of the arachidonate relaxation. These results suggest that in isolated coronaries, arachidonate undergoes a novel conversion, possibly by PG synthetase, to a dilating substance which exerts different contractile effects than exogenously administered PGE2, PGF2alpha and PGE1.
Authors:
P S Kulkarni; R Roberts; P Needleman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Prostaglandins     Volume:  12     ISSN:  0090-6980     ISO Abbreviation:  Prostaglandins     Publication Date:  1976 Sep 
Date Detail:
Created Date:  1976-12-01     Completed Date:  1976-12-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0320271     Medline TA:  Prostaglandins     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  337-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acids / pharmacology*
Arteries / drug effects
Aspirin / pharmacology
Cattle
Coronary Vessels / drug effects*
Dogs
Dose-Response Relationship, Drug
Drug Interactions
Humans
Indomethacin / pharmacology
Linolenic Acids / pharmacology
Meclofenamic Acid / pharmacology
Muscle Contraction / drug effects
Muscle, Smooth / drug effects
Oleic Acids / pharmacology
Prostaglandins E / administration & dosage,  pharmacology*
Prostaglandins F / administration & dosage,  pharmacology*
Vasodilator Agents / biosynthesis*
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Linolenic Acids; 0/Oleic Acids; 0/Prostaglandins E; 0/Prostaglandins F; 0/Vasodilator Agents; 50-78-2/Aspirin; 53-86-1/Indomethacin; 644-62-2/Meclofenamic Acid

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


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