Oxygen radicals in the nonvagal component of noncholinergic airway constriction.
To test the hypothesis that oxygen radicals play an important role in the nonvagal component of the noncholinergic bronchoconstriction in vivo, 37 guinea pigs weighing 329 +/- 8 g were randomly divided into five groups: group 1, vagotomy; group 2, vagotomy + CAT (catalase); group 3, vagotomy + SOD (superoxide dismutase); group 4, vagotomy + PBN (alpha-phenyl-N-tert-butyl nitrone); and group 5, capsaicin pretreatment. CAT, SOD, and PBN are antioxidants. Each animal was anesthetized, paralyzed, artificially ventilated, and pretreated with atropine and phenoxybenzamine. Immediately after acute capsaicin challenge, animals in group 1 exhibited decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, as well as an increase in functional residual capacity, indicating noncholinergic airway constriction. The bronchoconstriction was significantly ameliorated by SOD and PBN, and it was almost abolished by capsaicin pretreatment. Thirty minutes after acute capsaicin challenge, there was a significant decrease in airway NEP activity and an increase in lung substance P level in group 1 but not in other groups. These results indicate that nonvagal component of noncholinergic bronchoconstriction is partially modulated by oxygen radicals.
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001980:Bronchi / Q000201:enzymology / Q000294:innervation / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003497:Cyclic N-Oxides; D006168:Guinea Pigs; D008168:Lung / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism; D009589:Nitrogen Oxides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012129:Respiratory Function Tests; D013113:Spin Labels; D013373:Substance P / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014628:Vagotomy
D000975:Antioxidants; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013373:Substance P; C029217:phenyl-N-tert-butylnitrone; D002374:Catalase; D013482:Superoxide Dismutase; D015260:Neprilysin; D002211:Capsaicin