cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione.
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 approximately 1.2 microM) 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 microM 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.
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55906, USA.
W J
WJ
Perkins
C
C
Pabelick
D O
DO
Warner
K A
KA
Jones
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D026422:S-Nitrosoglutathione; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D026422:S-Nitrosoglutathione; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D005978:Glutathione; D006152:Cyclic GMP; D000109:Acetylcholine; D008751:Methylene Blue; D004229:Dithiothreitol