title: Abnormal endothelin B receptor vasomotor responses in patients with Hirschsprung's disease.
abstract: BACKGROUND
  Hirschsprung's disease is associated with defects in the endothelin-3 and endothelin B receptor genes.
  
  
  OBJECTIVE
  To assess the in vivo vasomotor responses to endothelin B receptor stimulation in patients with Hirschsprung's disease.
  
  
  METHODS
  Forearm blood flow was measured using venous occlusion plethysmography in 10 patients with Hirschsprung's disease and 10 matched healthy controls during intra-brachial infusion of the highly selective endothelin B receptor agonist, sarafotoxin S6c. To simulate endothelin B receptor dysfunction, sarafotoxin S6c was co-infused with the highly selective endothelin B receptor antagonist, BQ-788, in six of the healthy controls.
  
  
  RESULTS
  Sarafotoxin S6c caused a brief initial vasodilatation followed by a slow-onset, sustained vasoconstriction (p<0.001). Compared to control subjects, patients with Hirschsprung's disease had a substantial impairment of the initial vasodilatation whilst producing a more pronounced subsequent vasoconstriction (p<0.001). In healthy controls, co-infusion of BQ-788 and sarafotoxin S6c caused a similar pattern of responses to those obtained in patients with Hirschsprung's disease: abolition of the initial vasodilatation and augmentation of subsequent vasoconstriction (p<0.001).
  
  
  CONCLUSIONS
  In the majority of patients with Hirschsprung's disease, there is a functional defect of the vascular endothelin B receptor.
authors.affiliation: Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Edinburgh, UK. d.e.newby@ed.ac.uk
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.forename: F E
authors.initials: FE
authors.lastname: Strachan
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D065128:Endothelin Receptor Antagonists; D005260:Female; D005542:Forearm / Q000098:blood supply; D006627:Hirschsprung Disease / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*; D014757:Viper Venoms
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788