| Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate. | |
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MedLine Citation:
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PMID: 968049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P S Kulkarni; R Roberts; P Needleman |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Prostaglandins Volume: 12 ISSN: 0090-6980 ISO Abbreviation: Prostaglandins Publication Date: 1976 Sep |
Date Detail:
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Created Date: 1976-12-01 Completed Date: 1976-12-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0320271 Medline TA: Prostaglandins Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 337-53 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 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:
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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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