title: Reducing agents inhibit the contractile response of isolated guinea-pig main bronchi.
abstract: BACKGROUND
  Oxidants are involved in many respiratory disorders, including asthma and chronic obstructive pulmonary diseases. Reduced glutathione (GSH), one of the most important antioxidant compounds against oxidant free radicals, is particularly abundant in the respiratory epithelial lining fluid, where its concentration is increased in inflammatory disorders.
  
  
  OBJECTIVE
  We hypothesized that reducing agents may have a direct effect on airway smooth muscle. Therefore, we studied the effects of GSH on airway smooth muscle contractility in guinea-pig main bronchi. In parallel, we evaluated superoxide anion generation associated with in vitro bronchial smooth muscle contraction.
  
  
  METHODS
  Guinea-pig main bronchi were mounted in organ baths filled with Krebs-Henseleit solution. Concentration-response curves to acetylcholine (Ach) (10(-9)-10(-3) M), carbachol (10(-9)-10(-4) M), or histamine (10(-9)-10(-3) M) were performed in the presence or absence of either reduced or oxidized glutathione (GSSG) (10(-5)-10(-3) M). We also evaluated the effects of GSH and GSSG on allergen-induced contraction in main bronchi obtained from ovalbumin-sensitized guinea-pig. Superoxide dismutase (SOD)-inhibited cytochrome c reduction kinetics was performed to evaluate superoxide anion (O2-) production during Ach-induced contraction.
  
  
  RESULTS
  Reduced but not oxidized glutathione significantly decreased smooth muscle contraction induced by Ach, carbachol, and histamine. Similarly, only the reduced form of glutathione attenuated the bronchoconstriction induced by allergen exposure in bronchi from sensitized animals. Finally, SOD-inhibited cytochrome c reduction kinetics demonstrated increased O2- production following bronchial smooth muscle contraction. This production was not affected by epithelium removal.
  
  
  CONCLUSIONS
  Our findings show that GSH decreases bronchial smooth muscle contraction to different stimuli and that oxidant free radicals are produced during bronchial smooth muscle contraction. We suggest that oxidants are involved in the mechanisms of bronchoconstriction and that reducing agents could be a possible therapeutic option for airway obstruction sustained by bronchospasm.
authors.affiliation: Research Center on Asthma and COPD, University of Ferrara, Ferrera, Italy.
authors.forename: G L
authors.initials: GL
authors.lastname: Casoni
authors.forename: P
authors.initials: P
authors.lastname: Chitano
authors.forename: S
authors.initials: S
authors.lastname: Pinamonti
authors.forename: M
authors.initials: M
authors.lastname: Chicca
authors.forename: A
authors.initials: A
authors.lastname: Ciaccia
authors.forename: L
authors.initials: L
authors.lastname: Fabbri
authors.forename: A
authors.initials: A
authors.lastname: Papi
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology*; D019803:Glutathione Disulfide / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D013482:Superoxide Dismutase; D005978:Glutathione; D019803:Glutathione Disulfide