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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.
G L Casoni, and
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S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
October 1993,
European journal of pharmacology,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
May 1991,
European journal of pharmacology,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
January 1998,
Life sciences,
G L Casoni, and
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L Fabbri, and
A Papi
May 2001,
Respiratory medicine,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
February 1987,
Canadian journal of physiology and pharmacology,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
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A Papi
April 1985,
European journal of pharmacology,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
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European journal of pharmacology,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
September 1966,
Archives internationales de pharmacodynamie et de therapie,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
August 1991,
The American review of respiratory disease,
G L Casoni, and
P Chitano, and
S Pinamonti, and
M Chicca, and
A Ciaccia, and
L Fabbri, and
A Papi
November 1966,
The Journal of pharmacology and experimental therapeutics,
