Abstract
Hearts from Sprague-Dawley rats were perfused at constant flow and then exposed to 30 min global zero-flow ischemia followed by 15 min reperfusion. After ischemia-reperfusion, coronary arteries were dissected from the heart and segments 2 mm long were prepared for isometric tension recording in organ baths. Stimulation of the arteries with 5-hydroxytryptamine (10(-6) M) produced contraction, which was potentiated by treatment with endothelin-1 (3x10(-10); 10(-9) M). This potentiation was lower in the arteries from hearts after ischemia-reperfusion (for 3x10(-10) M, 15+/-5%; P>0.05; for 10(-9) M, 37+/-7%, P<0.01, n=5) than after control (for 3x10(-10) M, 34+/-4%; P<0.01; for 10(-9) M, 50+/-6%, P<0.01, n=5), and the potentiation was reduced by the inhibitor of nitric oxide synthesis l-NAME (10(-4) M), the antagonist of endothelin ET(A) receptors BQ123 (10(-6) M) and the antagonist of endothelin ET(B) receptors BQ788 (10(-6) M), but not by the cyclooxygenase inhibitor meclofenamate (10(-5) M). These results suggest that endothelin-1 at low concentrations potentiates coronary vasoconstriction, and this effect is reduced after ischemia-reperfusion, mediated by endothelin ET(A) and ET(B) receptors and dependent on nitric oxide release.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Animals
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Coronary Vessels / drug effects
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Coronary Vessels / enzymology
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Coronary Vessels / metabolism*
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Coronary Vessels / physiopathology
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Cyclooxygenase Inhibitors / pharmacology
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Endothelin A Receptor Antagonists
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Endothelin B Receptor Antagonists
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Endothelin-1 / metabolism*
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Enzyme Inhibitors / pharmacology
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In Vitro Techniques
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Male
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Meclofenamic Acid / pharmacology
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Myocardial Reperfusion Injury / metabolism*
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Myocardial Reperfusion Injury / physiopathology
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism
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Oligopeptides / pharmacology
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Peptides, Cyclic / pharmacology
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Perfusion
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Piperidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Endothelin A / metabolism
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Receptor, Endothelin B / metabolism
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Serotonin / pharmacology
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Vasoconstriction* / drug effects
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Vasoconstrictor Agents / pharmacology
Substances
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Cyclooxygenase Inhibitors
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Endothelin A Receptor Antagonists
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Endothelin B Receptor Antagonists
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Endothelin-1
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Enzyme Inhibitors
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Oligopeptides
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Peptides, Cyclic
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Piperidines
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Receptor, Endothelin A
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Receptor, Endothelin B
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Vasoconstrictor Agents
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Serotonin
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BQ 788
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Meclofenamic Acid
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Nitric Oxide Synthase
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cyclo(Trp-Asp-Pro-Val-Leu)
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NG-Nitroarginine Methyl Ester