Mechanism of H2O2-induced modulation of airway smooth muscle.
We investigated the effects of H2O2 generated by glucose (G) and glucose oxidase (GO) on the isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. H2O2 generated by G+GO was measured with luminol-dependent chemiluminescence. G+GO in the concentrations of 1x (1.80 microM G, 0.075 U/ml GO) and 2, 4, and 8x generated 1.35, 3.2, 6.10, and 6.00 microM of H2O2, respectively. H2O2 produced relaxation of rabbit tracheal smooth muscle, relaxed acetylcholine (ACh)-precontracted muscle, and reduced muscle responsiveness to ACh. These effects were concentration dependent. H2O2, however, produced contraction of guinea pig tracheal smooth muscle. Catalase completely inhibited the H2O2-induced relaxation of ACh-precontracted tracheal smooth muscle. H2O2-induced relaxation was greater in preparations with intact epithelium (65%) than in those denuded of epithelium (40%). The relaxant effects of H2O2 in the presence of an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), an inhibitor of guanylate cyclase (methylene blue), an inhibitor of cyclooxygenase (indomethacin), and an ATP-sensitive K+ channel blocker (glipizide) were 44, 44, 39, and 48%, respectively. H2O2-induced relaxation in the presence of indomethacin in preparations with denuded epithelium was 29%. These results suggest that H2O2-induced relaxation of tracheal smooth muscle is partly epithelium dependent and is mediated by inhibitory arachidonic acid metabolites, epithelium-derived relaxing factor (nitric oxide), ATP-sensitive K+ channels, and the synthesis and release of prostaglandins from epithelium and the underlying smooth muscle.
Gupta
J B
JB
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Prasad
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D005949:Glucose Oxidase / Q000494:pharmacology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D014132:Trachea / Q000187:drug effects*
D015221:Potassium Channels; D016718:Arachidonic Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D006152:Cyclic GMP; D005947:Glucose