ETA-dependent pressor effects and release of prostacyclin induced by endothelins in pulmonary and renal vasculature.
BQ-123, a selective endothelin A (ETA) receptor antagonist, was used to study the receptors involved in the ET-1-induced release of prostacyclin (PGI2) in perfused rat lung and rabbit kidney and the pressor effects of ET-1 in rabbit renal vasculature. In perfused rat lung, infusion of ET-1 (5 nM) significantly increased the release of PGI2, which was markedly reduced after a 15-min infusion of BQ-123 (1 microM). In rabbit kidney, the PGI2 release induced by ET-1 (10 nM) was abolished by a 15-min pretreatment with BQ-123 (1 microM). In both preparations the ET-1-induced release of PGI2 was fully restored 60 min after the interruption of BQ-123 infusion. In rabbit kidney a dose-dependent increase of perfusion pressure was also observed after bolus injections of ET-1 (5 and 10 pmol). The pressor responses to ET-1 were abolished by BQ-123 (0.1 microM), and 60 min after interruption of the infusion of the antagonist, the responses to ET-1 were restored to 68% and 99% of control values, respectively. Two selective ETB receptor agonists, IRL 1620 and BQ-3020, were inactive as pressor and prostanoid-releasing agents at doses and concentration 25-50 times higher than for ET-1 in perfused rabbit kidney. A higher concentration of BQ-123 (1 microM) did not modify the pressor responses to angiotensin II (5 nmol). Our results support the hypothesis that ET-1-induced release of vasodilatory prostanoids from perfused rat lung and rabbit kidney and constriction of rabbit renal vasculature are triggered by activation of ETA receptors.
D'Orléans-Juste
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Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
Yano
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Télémaque
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D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; D011464:Epoprostenol; C072247:cyclo(Trp-Asp-Pro-Val-Leu)