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

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.