Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary artery: role of thromboxane A(2).
To examine whether low concentrations of endothelin-1 potentiate the vasoconstrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10(-10) M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET(B) receptor antagonist (2,6-dimethylpiperidinecarbonyl-gamma-methyl-Leu-N(in)-[Methoxycarbonyl]-D-Trp-D-Nle) (BQ-788, 10(-6) M), but not the endothelin ET(A) receptor antagonist cyclo(D-Asp-Pro-D-Val-Leu-D-TRP) (BQ-123, 10(-6) M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor furegrelate and the thromboxane receptor antagonist [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino] methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10(-5) M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation. The Ca(2+) channel antagonist nifedipine (10(-6) M) did not affect the potentiation induced by endothelin-1. The results indicate that endothelin-1 potentiates the responses to electrical stimulation and noradrenaline by activating endothelin ET(B) receptors. This potentiation depends on the production of cyclooxygenase-generated factors, probably thromboxane A(2).
Department of Physiology, Facultad de Medicina y Odontologia, University of Valencia School of Medicine, Blasco Ibáñez, 17, 46010, Valencia, Spain. vila@post.uv.es
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Vila
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Medina
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Segarra
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Aldasoro
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Noguera
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Lluch
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology; D013928:Thromboxane A2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; C086539:BQ 788; D013928:Thromboxane A2; D009543:Nifedipine; D009638:Norepinephrine