US EPA

1501340 

Journal Article 

Hydrogen Sulphide-induced relaxation of porcine peripheral bronchioles 

Rashid, S; Heer, JK; Garle, MJ; Alexander, SP; Roberts, RE 

2013 

Yes 

British Journal of Pharmacology
ISSN: 0007-1188
EISSN: 1476-5381 

168 

8 

1902-1910 

English 

23215842 

10.1111/bph.12084 

WOS:000316809700012 

https://onlinelibrary.wiley.com/doi/10.1111/bph.12084
Exit
 

BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2) S) is an endogenous gasotransmitter. Although it has been shown to elicit responses in vascular and other smooth muscle preparations, a role for endogenously-produced H(2) S in mediating airway tone has yet to be demonstrated. Therefore, the aim of this study was to determine whether H(2) S is produced within the airways and to determine the functional effect on airway tone. EXPERIMENTAL APPROACH: Small peripheral airways (<5mm 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 H(2) S donor NaHS, or the precursor L-cysteine. H(2) S production from L-cysteine or 3-mercaptopyruvate in tissue homogenates was measured by the methylene blue assay. Expression of the H(2) S-synthesing enzymes cystathionine β-synthase (CBS), cystathionine γ lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST) were measured by Western blotting. KEY 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 H(2) S. Western blotting demonstrated immunoreactivity to CBS, CSE and 3-MST enzymes in the airways. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that H(2) S can be produced endogenously within porcine airways causing relaxation. The mechanism of relaxation depends, in part, on K(+) channel activity. 

hydrogen sulphide; airway smooth muscle; relaxation; K plus channels