title: EndothelinB receptor-mediated contraction of human and rat pulmonary resistance arteries and the effect of pulmonary hypertension on endothelin responses in the rat.
abstract: We investigated the endothelin (ET) receptor subtypes that mediate vasoconstriction in human and rat pulmonary resistance arteries and the effect of pulmonary hypertension on endothelin (ET)-induced contractile responses in rat vessels. In human vessels, sarafotoxin S6c (SXS6c) was more potent than ET-1, but its maximal contractile response was only 20-30% of that to ET-1. Responses to ET-1 were resistant to the ETA antagonist FR 139317, and another, BMS 182874, inhibited responses only to high concentrations of ET-1. In all rat vessels, ET-1, ET-3, and the ETB receptor agonist SXS6c showed the following order of potency: SXS6c = ET-3 > ET-1, and responses to SXS6c were inhibited by the ETB receptor antagonist BQ 788 (1 microM). Maximal responses to ET-1 were greatest in chronic hypoxic (CH) pulmonary-hypertensive rats. In control rats, responses to ET-1 were unaffected by FR 139317 (1 microM) and were potentiated by BMS 182874 (1 microM) and by the mixed ETA/ETB receptor antagonist bosentan (1 microM). A combination of BMS 182874 (10 microM) and the ETB receptor antagonist BQ 788 (1 microM) had no effect on responses to ET-1. In the CH rats, responses to ET-1 were unaffected by FR 139317, BMS 182874, or bosentan. The results suggest the presence of an inhibitory ETA receptor in these vessels that may inhibit ET-1 activation of ETB receptors, and also suggest that the influence of this inhibitory ETA receptor is reduced in CH rat vessels. The results indicate a role for ETB receptors in ET-1-mediated vasoconstriction in both human and rat pulmonary resistance arteries.
authors.affiliation: Division of Neuroscience and Biomedical Systems, Glasgow University, Scotland.
authors.forename: K M
authors.initials: KM
authors.lastname: McCulloch
authors.forename: M R
authors.initials: MR
authors.lastname: MacLean
mesh_terms: D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D016232:Endothelins; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788