Differential effects of nitric oxide synthesis on pulmonary vascular function during lung ischemia-reperfusion injury.
Lung ischemia-reperfusion (IR) injury causes alveolar, epithelial and endothelial cell dysfunction which often results in decreased alveolar perfusion, characteristic of an acute respiratory distress syndrome. Nitric oxide (NO) from endothelium-derived NO synthase (eNOS) helps maintain a low pulmonary vascular resistance. Paradoxically, during acute lung injury, overproduction of NO via inducible NO synthase (iNOS) and oxidative stress lead to reactive oxygen and nitrogen species (ROS and RNS) formation and vascular dysfunction. RNS potentiate vascular and cellular injury by oxidation, by decreasing NO bioavailability, and by regulating NOS isoforms. RNS potentiate their own production by uncoupling NO production through eNOS by oxidation and disruption of Akt-mediated phosphorylation of eNOS. This review focuses on effects of NO which cause vascular dysfunction in the unique environment of the lung and presents a hypothesis for interplay between eNOS and iNOS activation with implications for development of new strategies to treat vascular dysfunction associated with IR.
Sedoris
Kara C
KC
Department of Physiology and Biophysics, University of Louisville, KY 40292, USA.
Ovechkin
Alexander V
AV
Gozal
Evelyne
E
Roberts
Andrew M
AM
D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
D018841:HSP90 Heat-Shock Proteins; D007527:Isoenzymes; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt