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Nitric oxide protects against airway hyperresponsiveness
  1. P Kewin
  1. Wellcome Clinical Research Fellow, Department of Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK; pk49yclinmed.gla.ac.uk

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Nitric oxide (NO) is a highly active endogenous bronchodilator and, although increased levels are found in asthmatic lungs, the link between NO and asthma has remained elusive. NO is short lived in vivo but it reacts with cysteine sulphurs (thiols) in proteins to form more stable S-nitrosothiols (SNOs) which act as a source of bioactive NO. S-nitrosoglutathione (GSNO) is the most abundant SNO found in the airways where its levels are governed by the enzyme GSNO reductase (GSNOR). However, GSNO is depleted in asthmatic airways, suggesting a protective role.

In this study the authors showed that GSNOR levels were raised in the lungs of mice exposed to the allergen ovalbumin (OVA), probably due to lysis of airway epithelial cells and leucocytes. SNO levels were depleted. GSNOR gene knockout mice exposed to OVA had raised levels of SNOs in the airway, reduced basal airway tone, and no response to methacholine. Levels of type II inducible NO synthase were similar to wild type mice, as was the inflammatory response measured by bronchoalveolar fluid cell counts and IL-13, serum total IgE, and mucus metaplasia. Tracheal rings from wild type mice became desensitised to repeated β adrenergic stimulation, whereas GSNOR knockout mice did not and so retained the capacity to relax.

This is the first study to show a definitive link between NO and airway hyperresponsiveness (AHR). NO, when present as SNOs, protects against AHR through modulation of β adrenoreceptor function. SNO levels are regulated by GSNOR which is raised in asthmatic airways, and the resulting lack of SNOs promotes AHR.

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