L-NAME aggravates pulmonary oxygen toxicity in rats.
Exposure to high oxygen concentration leads to acute lung injury and death in rats after 72 h. The pathophysiology of this phenomenon relies on several mechanisms, including alteration of vascular reactivity, recruitment and activation of neutrophils and alveolar macrophages, production of cytokines and excess production of free radicals. In addition to its potent vasodilating effect, nitric oxide (NO) has also been reported to prevent free radical-mediated damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to continuous high oxygen concentration, we studied the effect of administration of 50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to oxygen and injected with L-NAME died within 60 h as compared to 22% of the animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and bronchoalveolar lavage fluid protein were also significantly increased in animals exposed to oxygen and receiving L-NAME. The lung water content was higher in the oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05). Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p < 0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a deleterious effect in rats exposed to hyperoxia, which might suggest that endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary lesions.
Capellier
G
G
CHU Jean Minjoz, Besançon, France.
Maupoil
V
V
Boillot
A
A
Kantelip
J P
JP
Rochette
L
L
Regnard
J
J
Barale
F
F
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester