title: The role of cGMP in the relaxation to nitric oxide donors in airway smooth muscle.
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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: K
authors.initials: K
authors.lastname: Stuart-Smith
authors.forename: D O
authors.initials: DO
authors.lastname: Warner
authors.forename: K A
authors.initials: KA
authors.lastname: Jones
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007537:Isometric Contraction / Q000187:drug effects*; D008751:Methylene Blue / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide; D013552:Swine
chemical_list: D000634:Aminoquinolines; D000931:Antidotes; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue