title: Does blockade of endothelinB1-receptor activation increase endothelinB2/endothelinA receptor-mediated constriction in the rabbit basilar artery?
abstract: The purpose of this study was to investigate whether endothelin (ET)-1 activation of ETB1 receptors influences the relative magnitude of ETA/ETB2 receptor-mediated ET-1 constriction in the rabbit basilar artery. Initial challenge of ET-1-constricted vessels with BQ610, an ETA-receptor antagonist, resulted in approximately 60% relaxation, and subsequent addition of BQ788, an ETB1/2-receptor antagonist, relaxed the remaining constriction. To test whether blockade of ETB1 receptors influenced the relative magnitude of ETA/ETB2 receptor-mediated constriction, ET-1-constricted vessels were exposed to RES-701-1, an ETB1-receptor antagonist, before challenge with BQ610 or BQ788. RES-701-1 enhanced the ET-1 constriction by approximately 60%, consistent with blockade of ETB1 receptor-mediated endothelium-dependent relaxation. In ET-1-constricted vessels treated with RES-701-1, BQ610 challenge resulted in complete relaxation, whereas BQ788 was without effect. However, when 10 nM acetylcholine was added to RES-701-1-treated ET-1-constricted vessels, (a) BQ610 challenge resulted in only approximately 30% relaxation, and subsequent BQ788 addition relaxed the remaining constriction; and (b) BQ788 challenge resulted in approximately 35% relaxation, and subsequent BQ610 addition relaxed the remaining constriction. Acetylcholine induced approximately 10% relaxation of RES-701-1-treated ET-1-constricted vessels. It is speculated that a dynamic relation exists between ETA and ETB2 receptor-mediated constriction, such that ET-1-induced ETB2 receptor-mediated constriction of the basilar artery is dependent on ETB1 receptor activation and, in the absence of this activation, the constriction reverts to completely ETA receptor mediated.
authors.affiliation: Department of Neurosurgery, University of Cincinnati College of Medicine, OH 45267-0575, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zuccarello
authors.forename: R
authors.initials: R
authors.lastname: Boccaletti
authors.forename: R M
authors.initials: RM
authors.lastname: Rapoport
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C087220:BQ 610; C087120:RES 701-1; C086539:BQ 788; D000109:Acetylcholine