title: Endothelin-1 potentiation of coronary artery contraction after ischemia-reperfusion.
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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain. angeluis.villalon@uam.es
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: Yesika María
authors.initials: YM
authors.lastname: Amezquita
authors.forename: Luis
authors.initials: L
authors.lastname: Monge
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández
authors.forename: Adely
authors.initials: A
authors.lastname: Salcedo
authors.forename: Godofredo
authors.initials: G
authors.lastname: Diéguez
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; D012701:Serotonin; C086539:BQ 788; D008469:Meclofenamic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester