Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice

Maroun J. Mhanna, Tom Ferkol, Richard J. Martin, Ismail A. Dreshaj, Anna M. Van Heeckeren, Tom J. Kelley, Musa A. Haxhiu

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The pulmonary disease of cystic fibrosis (CF) is characterized by persistent airway obstruction, which has been attributed to chronic endobronchial infection and inflammation. The levels of exhaled nitric oxide (NO) are reduced in CF patients, which could contribute to bronchial obstruction through dysregulated constriction of airway smooth muscle. Because airway epithelium from CF mice has been shown to have reduced expression of inducible NO synthase, we examined airway responsiveness and relaxation in isolated tracheas of CF mice. Airway relaxation as measured by percent relaxation of precontracted tracheal segments to electrical field stimulation (EFS) and substance P, a nonadrenergic, noncholinergic substance, was significantly impaired in CF mice. The airway relaxation in response to prostaglandin E2 was similar in CF and non-CF animals. Treatment with the NO synthase inhibitor NG-nitro-L-arginine methylester reduced tracheal relaxation induced by EFS in wild-type animals but had virtually no effect in the CF mice. Conversely, exogenous NO and L-arginine, a NO substrate, reversed the relaxation defect in CF airway. We conclude that the relative absence of NO compromises airways relaxation in CF, and may contribute to the bronchial obstruction seen in the disease.

Original languageEnglish
Pages (from-to)621-626
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume24
Issue number5
DOIs
StatePublished - Jan 1 2001

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