title: Analysis of ET-A and ET-B receptors using an isolated perfused rat lung preparation.
abstract: OBJECTIVE
  The pulmonary and vascular effects of endothelin-1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin-1 (ET-1) and the endothelin B (ET(B)) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET(A))-receptor antagonist FR 139317, the ET(B)-receptor antagonist BQ 788 and the combined ET(A)/ET(B)-receptor antagonist Bosentan. The respiratory parameter airway conductance (G(aw)) and the vascular parameter perfusion flow were analysed simultaneously.
  
  
  RESULTS
  Concentration-response curves for ET-1 administered intra-arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET-1, given as a bolus dose intra-arterially (100 microL of 0.2 nM), induced a strong- and long-lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G(aw) or perfusion flow. FR 139317 reduced the effect of ET-1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET-1 while G(aw) was not influenced. The combined ET(A)/ET(B) antagonist Bosentan powerfully prevented the ET-1-induced decrease in G(aw) but did not alter its reduction in perfusion flow.
  
  
  CONCLUSIONS
  The potent effect of ET-1 on the vascular side of the lung is mediated mainly through ET(A) receptors, whereas both ET(A) and ET(B) receptors are involved in G(aw) in the rat lung.
authors.affiliation: Department of Internal Medicine, Lund University Hospital, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Granström
authors.forename: E
authors.initials: E
authors.lastname: Nilsson
authors.forename: U
authors.initials: U
authors.lastname: Hultkvist-Bengtsson
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D000077300:Bosentan; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001381:Azepines; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317; C086539:BQ 788; D000077300:Bosentan