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  • Title: The role of cGMP in the relaxation to nitric oxide donors in airway smooth muscle.
    Author: Stuart-Smith K, Warner DO, Jones KA.
    Journal: Eur J Pharmacol; 1998 Jan 12; 341(2-3):225-33. PubMed ID: 9543243.
    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-1) 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 microM), both sodium nitroprusside and diethylamine-NO caused relaxation and an increase in [cGMP]i. By contrast, SIN-1 caused a relaxation which was not associated with a concomitant increase in [cGMP]i. Methylene blue (10 microM) and LY83583 (10 microM) 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.
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