title: Hydrogen sulphide-induced relaxation of porcine peripheral bronchioles.
abstract: OBJECTIVE
  Hydrogen sulphide (H2S) is an endogenous gasotransmitter. Although it has been shown to elicit responses in vascular and other smooth muscle preparations, a role for endogenously produced H2S in mediating airway tone has yet to be demonstrated. Therefore, the aim of this study was to determine whether H2S is produced within the airways and to determine the functional effect on airway tone.
  
  
  METHODS
  Small peripheral airways (<5 mm in diameter) from porcine lungs were set up in isolated tissue baths, pre-contracted with the muscarinic agonist carbachol, and then exposed to either the H2S donor sodium hydrosulphide (NaHS), or the precursor L-cysteine. H2S production from L-cysteine or 3-mercaptopyruvate in tissue homogenates was measured by the methylene blue assay. Expression of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) were measured by Western blotting.
  
  
  RESULTS
  NaHS caused a large relaxation of the airways, which was inhibited partially by pre-contraction with KCl or exposure to tetraethylammonium, but not glibenclamide, paxilline or 4-aminopyridine. L-cysteine also caused a relaxation of the airways which was inhibited by the CBS inhibitor aminooxyacetic acid. Tissue homogenates from airways exposed to L-cysteine or 3-mercaptopyruvate in vitro showed a significant production of H2S. Western blotting demonstrated immunoreactivity to CBS, CSE and 3-MST enzymes in the airways.
  
  
  CONCLUSIONS
  These data demonstrate that H2S can be produced endogenously within porcine airways causing relaxation. The mechanism of relaxation depends, in part, on K(+) channel activity.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rashid
authors.forename: J K
authors.initials: JK
authors.lastname: Heer
authors.forename: M J
authors.initials: MJ
authors.lastname: Garle
authors.forename: S P H
authors.initials: SP
authors.lastname: Alexander
authors.forename: R E
authors.initials: RE
authors.lastname: Roberts
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D015221:Potassium Channels / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology; D013466:Sulfurtransferases / Q000378:metabolism; D013552:Swine
chemical_list: D015221:Potassium Channels; D013440:Sulfides; D002217:Carbachol; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D003545:Cysteine; D006862:Hydrogen Sulfide