ENDOGENOUS NITROGEN-OXIDES AND BRONCHODILATOR S-NITROSOTHIOLS IN HUMAN AIRWAYS

Recent discoveries suggesting essential bioactivities of nitric oxide (NO.) in the lung are difficult to reconcile with the established pulm onary cytotoxicity of this common air pollutant. These conflicting obs ervations suggest that metabolic intermediaries may exist in the lung to modulate the bioactivity and toxicity of NO.. We report that S-nitr osothiols (RS-NO), predominantly the adduct with glutathione, are pres ent at nano- to micromolar concentrations in the airways of normal sub jects and that their levels vary in different human pathophysiologic s tates. These endogenous RS-NO are long-lived, potent relaxants of huma n airways under physiological O2 concentrations. Moreover, RS-NO form in high concentrations upon administration of NO. gas. Nitrite (10-20 muM) is found in airway lining fluid in concentrations linearly propor tional to leukocyte counts, suggestive of local NO. metabolism. NO. it self was not detected either free in solution or in complexes with tra nsition metals. These observations may provide insight into the means by which NO. is packaged in biological systems to preserve its bioacti vity and limit its potential O2-dependent toxicity and suggest an impo rtant role for NO. in regulation of airway luminal homeostasis.