Enhanced response of pig coronary arteries to endothelin-1 after ischemia-reperfusion. Role of endothelin receptors, nitric oxide and prostanoids.
To analyse the coronary effects of endothelin-1 after ischemia-reperfusion, the left anterior descending coronary artery of anesthetized pigs was subjected to 30-min occlusion followed by 60-min reperfusion. Then, rings distal (ischemic arteries) and proximal (control arteries) to the occlusion were taken from this artery and prepared for isometric tension recording. The sensitivity of the contraction in response to endothelin-1 (3 x 10(-10)-3 x 10(-7) M) and the endothelin ET(B) receptor agonist IRL-1620 (3 x 10(-10)-3 x 10(-7) M) was greater in ischemic vessels. The endothelin ET(A) receptor antagonist BQ-123 (10(-7)-3 x 10(-6) M) decreased the sensitivity of the response to endothelin-1 similarly in ischemic and control arteries. The endothelin ET(B) receptor antagonist BQ-788 (10(-6) M), endothelium removal or the inhibitor of nitric oxide synthesis N(omega)-nitro-L-arginine methyl ester (L-NAME 10(-4) M) potentiated the response to endothelin-1 and IRL-1620 in control arteries only. The cyclooxygenase inhibitor meclofenamate (10(-5) M) augmented the maximal response to endothelin-1 in control arteries, and reduced it in ischemic arteries. In precontracted arteries, IRL-1620 (3 x 10(-11)-3 x 10(-10) M) relaxed control but not ischemic arteries, and L-NAME or meclofenamate abolished this relaxation. Therefore, ischemia-reperfusion increases the coronary vasoconstriction in response to endothelin-1 probably due to impairment of endothelin ET(B) receptor-induced release of nitric oxide and prostacyclin, augmentation of the contractile response to activation of endothelin ET(B) receptors, and increased release of vasoconstrictor prostanoids.
Climent
Belén
B
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Fernández
Nuria
N
Sanz
Elena
E
Sánchez
Ana
A
Monge
Luis
L
García-Villalón
Angel Luis
AL
Diéguez
Godofredo
G
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D044022:Receptor, Endothelin A / Q000819:agonists / Q000502:physiology; D044023:Receptor, Endothelin B / Q000819:agonists / Q000502:physiology; D017466:Receptors, Endothelin / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D011453:Prostaglandins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; C074308:sovateltide; D009599:Nitroprusside; D009569:Nitric Oxide; C086539:BQ 788; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester