期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 108, 期 2, 页码 198-204出版社
MOSBY-ELSEVIER
DOI: 10.1067/mai.2001.116572
关键词
asthma; airway hyperresponsiveness; allergen; ecNOS; nNOS; iNOS; nitric oxide; bradykinin
Background: Eudogenous 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 ox:ide 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 or 3 periods (1 diluent and 2 allergen challenges). AHR to bradylkinin (PD20BK) 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 (PD20BK, 70.8 nmol [range, 6.3-331] and 257 nmol [35.5-2041], respectively; P=.0004). After L-NMMA, preallergen and postallergen PD20BK 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据