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Role of nitric oxide and superoxide in allergen‐induced airway hyperreactivity after the late asthmatic reaction in guinea‐pigs
Author(s) -
Boer Jacob de,
Meurs Herman,
Flendrig Leonard,
Koopal Miranda,
Zaagsma Johan
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704191
Subject(s) - ovalbumin , methacholine , nitric oxide , histamine , guinea pig , superoxide , immunology , in vivo , allergen , chemistry , superoxide dismutase , nitric oxide synthase , endocrinology , medicine , allergy , biology , biochemistry , lung , respiratory disease , enzyme , oxidative stress , immune system , microbiology and biotechnology
In the present study, the roles of nitric oxide (NO) and superoxide anions (O 2 − ) in allergen‐induced airway hyperreactivity (AHR) after the late asthmatic reaction (LAR) were investigated ex vivo , by examining the effects of the NO synthase inhibitor N ω ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) and superoxide dismutase (SOD) on the responsiveness to methacholine of isolated perfused guinea‐pig treacheae from unchallenged (control) animals and from animals 24 h after ovalbumin challenge. At 24 h after allergen challenge, the animals developed AHR in vivo , as indicated by a mean 2.63±0.54 fold ( P <0.05) increase in sensitivity to histamine inhalation. Compared to unchallenged controls, tracheal preparations from the ovalbumin‐challenged guinea‐pigs displayed a significant 1.8 fold ( P <0.01) increase in the maximal response (E max ) to methacholine, both after intraluminal (IL) and extraluminal (EL) administration of the agonist. No changes were observed in the sensitivity (pEC 50 ) to the agonist. Consequently, the ΔpEC 50 (EL‐IL), as a measure of epithelial integrity, was unchanged. In the presence of L ‐NAME (100 μ M , IL), tracheae from control guinea‐pigs showed a 1.6 fold ( P <0.05) increase in the E max of IL methacholine. By contrast, the E max of IL methacholine was significantly decreased in the presence of 100 u ml −1 EL SOD (54% of control, P <0.01). Remarkably, the increased responsiveness to IL methacholine at 24 h after allergen challenge was reversed by L ‐NAME to control ( P <0.01), and a similar effect was observed with SOD ( P <0.01). The results indicate that both NO and O 2 − are involved in the tracheal hyperreactivity to methacholine after the LAR, possibly by promoting airway smooth muscle contraction through the formation of peroxynitrite.British Journal of Pharmacology (2001) 133 , 1235–1242; doi: 10.1038/sj.bjp.0704191