Since the discovery of nitric oxide (NO), an intracellular signal transmitter, the role of NO has been investigated in various organs. In the respiratory system, NO derived from the constitutive type of NO synthase (cNOS, NOS1, NOS3) induces bronchodilation and pulmonary vasodilatation to maintain homeostasis. In contrast, the roles of excessive NO derived from the inducible type of NOS (iNOS, NOS2) in airway and lung inflammation in inflammatory lung diseases including bronchial asthma and chronic obstructive pulmonary disease (COPD) are controversial. In these inflammatory lung diseases, excessive nitrosative stress has also been observed. In asthma, some reports have shown that nitrosative stress causes airway inflammation, airway hyperresponsiveness, and airway remodeling, which are the features of asthma, whereas others have demonstrated the anti-inflammatory role of NO derived from NOS2. In the case of refractory asthma, more nitrosative stress has been reported to be observed in such airways compared with that in well-controlled asthmatics. In COPD, reactive nitrogen species (RNS), which are NO and NO-related molecules including nitrogen dioxide and peroxynitrite, cause lung inflammation, oxidative stress, activation of matrix metalloproteinase, and inactivation of antiprotease, which are involved in the pathophysiology of the disease. In the present paper, we review the physiological and pathophysiological effects of NO and NO-related molecules in the respiratory system and in inflammatory lung diseases.
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