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

William J. Perkins, Christina Pabelick, David O. Warner, Keith A. Jones

Research output: Contribution to journalArticle

42 Scopus citations

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](i) induced by 1 and 10 μM GSNO, but isometric force decreased by 10 ± 4 and 55 ± 3%, respectively. After recovery of [cGMP](i) to 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.

Original languageEnglish (US)
Pages (from-to)C468-C474
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number2 44-2
DOIs
StatePublished - Aug 1998

Keywords

  • Canine lung
  • Canine trachea
  • DL-dithiothreitol
  • Guanosine 3',5'-cyclic monophosphate
  • Nitric oxide
  • Sulfhydryl reagents

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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