cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione.

Academic Article

Abstract

  • This study tested the hypothesis that the NO donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) in part by a cGMP-independent process that involves reversible oxidation of intracellular thiols. GSNO caused a concentration-dependent relaxation in ACh-contracted strips (EC50∼1.2 μM) accompanied by a concentration-dependent increase in cytosolic cGMP concentration ([cGMP]i). The soluble guanylate cyclase inhibitor methylene blue prevented the increase in [cGMP]iinduced by 1 and 10 μM GSNO, but isometric force decreased by 10 ± 4 and 55 ± 3%, respectively. After recovery of [cGMP]ito baseline, GSNO-induced relaxation persisted during continuous ACh stimulation. Dithiothreitol caused a rapid recovery of isometric force to values similar to those obtained with ACh alone in these strips. We conclude that GSNO relaxes CTSM contracted by ACh in part by oxidation of intracellular protein thiols.
  • Authors

    Keywords

  • canine lung, canine trachea, dl-dithiothreitol, guanosine 3′,5′-cyclic monophosphate, nitric oxide, sulfhydryl reagents
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20730830
  • Author List

  • Perkins WJ; Pabelick C; Warner DO; Jones KA
  • Start Page

  • C468
  • End Page

  • C474
  • Volume

  • 275
  • Issue

  • 2