L-arginine enhances injury in the isolated rabbit lung during hyperoxia.
L-Arginine is the substrate for synthesis of nitric oxide (NO.) by NO synthase which physiologically produces vasodilation. The reaction of NO. or its metabolites with O2 or its metabolites, however, can produce toxic reactive species which may cause cellular injury. We hypothesized that excessive NO. production in isolated perfused rabbit lungs at elevated PO2 could support the production of toxic nitrogen metabolites. In isolated perfused rabbit lungs ventilated with 95% O2, 1.0 mM L-arginine caused significant pulmonary hypertension and edema. These effects of L-arginine were attenuated by the NO. synthase inhibitor, L-NAME (0.5 mM), not affected by SOD pretreatment (100 u/ml) and reversed by pretreatment with catalase (200 u/ml), suggesting a mechanism involving H2O2. This mechanism was supported by producing L-arginine mediated injury in normoxic lungs in the presence of a H2O2 generating system. This injury also was attenuated by L-NAME. On the basis of these results, we conclude that H2O2 interacts with NO. or one of its oxidized metabolites to contribute to acute lung injury during hyperoxia. Such a mechanism may involve peroxynitrite anion, although direct proof of its formation is lacking under these conditions.
Nozik
E S
ES
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Huang
Y C
YC
Piantadosi
C A
CA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure; D002374:Catalase / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D014655:Vascular Resistance
D005609:Free Radicals; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001120:Arginine; D006861:Hydrogen Peroxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester