Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 533, Issue 1-3, Pages 240-252Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2005.12.057
Keywords
nitric oxide; oxidant; peroxynitrite; nitrosative stress; asthma; COPD (chronic obstructive pulmonary diseases)
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Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of airway functions. In response to various stimuli activated inflammatory cells (e.g., eosinophils and neutrophils) generate oxidants (oxidative stress) which in conjunction with exaggerated enzymatic release of NO and augmented NO metabolites produce the formation of strong oxidizing reactive nitrogen species, such as peroxynitrite, in various airway diseases including asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and acute respiratory distress syndrome (ARDS). Reactive nitrogen species provoke amplification of inflammatory processes in the airways and lung parenchyma causing DNA damage, inhibition of mitochondrial respiration, protein dysfunction and cell damage (nitrosative stress). These effects alter respiratory homeostasis (such as bronchomotor tone and pulmonary surfactant activity) and the long-term persistence of nitrosative stress may contribute to the progressive deterioration of Pulmonary functions leading to respiratory failure. Recent studies showing that protein nitration can be dynamic and reversible (denitration mechanisms) open new horizons in the treatment of chronic respiratory diseases affected by the deleterious actions of nitrosative stress. (c) 2005 Elsevier B.V. All rights reserved.
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