Modulation of nitric oxide pathways: therapeutic potential in asthma and chronic obstructive pulmonary disease

Nitric oxide (NO) is present in the exhaled breath of humans and other mammalian species. It is generated in the lower airways by enzymes of the nitric oxide synthase (NOS) family, although nonenzymatic synthesis and consumptive processes may also influence levels of NO in exhaled breath. The biological properties of NO in the airways are multiple, complex, and bidirectional. Under physiological conditions, NO appears to play a homeostatic bronchoprotective role. However, its proinflammatory properties could also potentially cause tissue injury and contribute to airway dysfunction in disease states such as asthma and chronic obstructive pulmonary disease (COPD). This article will review the physiological and pathophysiological roles of NO in the airways, discuss the rationale for the use of drugs that modulate NO pathways--nitric oxide synthase inhibitors and NO donors--to treat inflammatory airway diseases, and attempt to predict the likely therapeutic benefit of such agents.