The role of cGMP in the relaxation to nitric oxide donors in airway smooth muscle

Karen Stuart-Smith, David O. Warner, Keith A. Jones

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The aim of this study was to determine the effect of the soluble guanylyl cyclase inhibitors methylene blue and LY83583 (6-anilino-5,8- quinolinedione) on relaxation and increases in intracellular guanosine 3',5'- cyclic monophosphate (cGMP) concentration ([cGMP](i)) induced by sodium nitroprusside, 3-morpholinosydnonimine (SIN-I) and diethylamine-nitric oxide (NO) in porcine tracheal smooth muscle in vitro. We measured (1) the effect of NO donors on isometric force and [cGMP](i) and (2) the ability of methylene blue and LY83583 to antagonize these effects. In muscle strips contracted with carbachol (0.1-0.3 μM), both sodium nitroprusside and diethylamine-NO caused relaxation and an increase in [cGMP](i). By contrast, SIN-I caused a relaxation which was not associated with a concomitant increase in [cGMP](i). Methylene blue (10 μM) and LY83583 (10 μM) completely blocked the increase in [cGMP](i) induced by sodium nitroprusside and diethylamine-NO; however substantial relaxation remained. It is concluded that in porcine airway smooth muscle, (1) relaxation induced by some NO donors may occur without a concomitant increase in [cGMP]i; and (2) whereas relaxation induced by some NO donors may be associated with increases in [cGMP](i), the relaxation is not completely dependent upon it.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalEuropean Journal of Pharmacology
Volume341
Issue number2-3
DOIs
StatePublished - Jan 12 1998

Keywords

  • 3-Morpholinosydnonimine
  • Airway
  • CGMP
  • Diethylamine-nitric oxide
  • LY83583
  • Methylene blue
  • Nitric oxide (NO)
  • Smooth muscle
  • Sodium nitroprusside

ASJC Scopus subject areas

  • Pharmacology

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