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This Article Full Text (PDF) Free All Versions of this Article: chest.06-3046v1 132/2/581    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brindicci, C. Articles by Kharitonov, S. A. Search for Related Content PubMed PubMed Citation Articles by Brindicci, C. Articles by Kharitonov, S. A.

Effect of an inducible nitric oxide synthase inhibitor on differential flow exhaled nitric oxide in asthmatic patients and healthy volunteers

Section of Airway Diseases, National Heart and Lung Institute, Imperial College, London, United Kingdom

s.kharitonov{at}imperial.ac.uk

Abstract

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (J_NO, pL/sec) produced in the large airways is due to an enzyme over expression, we administered a relative selective iNOS inhibitor, aminoguanidine, by nebulisation in a double-blind, placebo-controlled manner in asthmatic and normal subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in peripheral lungs (C_alv, ppb) or on diffusion of NO in the airways (D_NO, pL/s^-1ppb^-1). Aminoguanidine resulted in a significant reduction in J_NO compared with saline control in eight normal subjects and in eight patients with asthma but caused no significant changes in C_alv or in D_NO in either group. No rise in blood pressure, fall in FEV₁ or adverse effects were observed in either group of subjects. These results indicate that iNOS from larger airways is the predominant source of elevated large airway derived NO in asthma, and that exhaled NO from peripheral lungs is not affected by nebulised iNOS inhibitor and therefore more likely derived form constitutive forms of NOS.

Key Words: nitric oxide • different flow rates • nitric oxide inhibitor • small airways