Two faces of nitric oxide: implications for cellular mechanisms of oxygen toxicity.
Recent investigations have elucidated some of the diverse roles played by reactive oxygen and nitrogen species in events that lead to oxygen toxicity and defend against it. The focus of this review is on toxic and protective mechanisms in hyperoxia that have been investigated in our laboratories, with an emphasis on interactions of nitric oxide (NO) with other endogenous chemical species and with different physiological systems. It is now emerging from these studies that the anatomical localization of NO release, which depends, in part, on whether the oxygen exposure is normobaric or hyperbaric, strongly influences whether toxicity emerges and what form it takes, for example, acute lung injury, central nervous system excitation, or both. Spatial effects also contribute to differences in the susceptibility of different cells in organs at risk from hyperoxia, especially in the brain and lungs. As additional nodes are identified in this interactive network of toxic and protective responses, future advances may open up the possibility of novel pharmacological interventions to extend both the time and partial pressures of oxygen exposures that can be safely tolerated. The implications of a better understanding of the mechanisms by which NO contributes to central nervous system oxygen toxicity may include new insights into the pathogenesis of seizures of diverse etiologies. Likewise, improved knowledge of NO-based mechanisms of pulmonary oxygen toxicity may enhance our understanding of other types of lung injury associated with oxidative or nitrosative stress.
Duke University Medical Center Center for Hyperbaric Medicine and Environmental Physiology, Durham, NC 27710, USA. barry.w.allen@duke.edu
Barry W
BW
Allen
Ivan T
IT
Demchenko
Claude A
CA
Piantadosi
D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004242:Diving / Q000009:adverse effects; D006801:Humans; D006931:Hyperbaric Oxygenation / Q000009:adverse effects; D018496:Hyperoxia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D010100:Oxygen