Document Detail

Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma.
MedLine Citation:
PMID:  11496234     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Endogenous nitric oxide protects against airway hyperresponsiveness (AHR) to bradykinin in mild asthma, whereas AHR to bradykinin is enhanced by inhaled allergens. OBJECTIVE: Hypothesizing that allergen exposure impairs bronchoprotective nitric oxide within the airways, we studied the effect of the inhaled nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on AHR to bradykinin before and after allergen challenge in 10 subjects with atopic asthma. METHODS: The study consisted of 3 periods (1 diluent and 2 allergen challenges). AHR to bradykinin (PD(20)BK) was examined before and 48 hours after allergen challenge, both after double-blinded pretreatment with L-NMMA or placebo. The accompanying expression of the various NOS isoforms (ecNOS, nNOS, and iNOS) was examined by means of immunohistochemistry in bronchial biopsies obtained after diluent and allergen challenge. RESULTS: After placebo, AHR to BK worsened after allergen challenge in comparison with before allergen challenge (PD(20)BK, 70.8 nmol [range, 6.3-331] and 257 nmol [35.5-2041], respectively; P =.0004). After L-NMMA, preallergen and postallergen PD(20)BK values (50.1 nmol [1.8-200] vs 52.5 nmol [6.9-204]; P =.88) were similarly reduced (P <.01) and not different from the postplacebo/postallergen value (P >.05). After allergen challenge, the intensity of staining in bronchial epithelium decreased for ecNOS (P =.03) and increased for iNOS (P =.009). These changes in immunostaining were correlated with the accompanying worsening in AHR to BK (R(s) = -0.66 and 0.71; P <.04). CONCLUSIONS: These data indicate that allergen exposure in asthma induces increased airway hyperresponsiveness to bradykinin through impaired release of bronchoprotective nitric oxide associated with downregulation of ecNOS. This suggests that new therapeutic strategies towards restoring the balance among the NOS isoforms during asthma exacerbations are warranted.
F L Ricciardolo; M C Timmers; P Geppetti; A van Schadewijk; J J Brahim; J K Sont; H W de Gouw; P S Hiemstra; J H van Krieken; P J Sterk
Related Documents :
2915184 - Lung mucociliary transport in asymptomatic asthma: effects of inhaled histamine.
10989864 - Successful pharyngeal pulse oximetry in low perfusion states.
1771604 - Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapn...
6396294 - Calcium channel blocking agents in bronchial hyperreactivity.
11496234 - Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma.
23541104 - Influence of exercise order on muscle damage during moderate-intensity resistance exerc...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  108     ISSN:  0091-6749     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-09     Completed Date:  2001-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  198-204     Citation Subset:  AIM; IM    
Department of Pulmonology, Leiden University Medical Center, The Netherlands.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Allergens / immunology*
Asthma / immunology*
Bradykinin / immunology*
Bronchi / immunology*
Hypersensitivity, Immediate / immunology
Isoenzymes / isolation & purification
Nitric Oxide / biosynthesis*
Nitric Oxide Synthase / isolation & purification
omega-N-Methylarginine / pharmacology
Reg. No./Substance:
0/Allergens; 0/Isoenzymes; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 58-82-2/Bradykinin; EC Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression whi...
Next Document:  Basophil recruitment and IL-4 production during human allergen-induced late asthma.