Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung.
Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.
Arkovitz
M S
MS
Division of Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Szabó
C
C
Garcia
V F
VF
Wong
H R
HR
Wispé
J R
JR
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004790:Enzyme Induction; D005260:Female; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008170:Lung Compliance / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase