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.
Redington
Anthony E
AE
Department of Respiratory Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, United Kingdom. anthony.redington@nwlh.nhs.uk
D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D001944:Breath Tests; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D012137:Respiratory System / Q000201:enzymology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase