Airway Thiol-NO Adducts as Determinants of Exhaled NO.

Thiol-NO adducts such as -nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway -nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (F) is associated with asthmatic airway inflammation. We hypothesized that F could reflect airway -nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway -nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary -nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase ) unable reductively to catabolize GSNO. More NO was produced from GSNO in the compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases F using an inhalational challenge model in normal human subjects. F increased in all subjects tested, with a median t of 32.0 min. Taken together, these data demonstrate that F reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, F following a GSNO challenge could be a non-invasive test for airway GSNO catabolism.