Ca(2+)-dependent and Ca(2+)-independent exhaled nitric oxide, presence in germ-free animals, and inhibition by arginine analogues.
Nitric oxide (NO) was detected by chemiluminescence in exhaled air from awake humans, anaesthetized rabbits, guinea pigs, germ-free rats and conventional rats. Rabbits exhibited the highest concentrations, followed by guinea pigs, humans and rats. There was no significant difference between germ-free rats and control rats. The authenticity of NO was confirmed in cold-trap experiments. Intravenous administration of inhibitors of NO synthase (0.01-300 mg kg-1) to guinea pigs dose dependently reduced NO concentrations in exhaled air with the following potency order: L-N omega-nitro-arginine-methylester > asymmetric NG,NG-dimethyl-L-arginine-dihydrochloride = L-NG-mono-methyl -arginine = L-N5- (1-iminoethyl)-ornithine = aminoguanidine > L-canavanine. The effect of the NO synthase inhibitors was partly or fully reversed by L-arginine (1 g kg-1 i.v.), and L-arginine per se induced a significant increment of NO in exhaled air. In rats, L-N omega-nitro-arginine-methylester was considerably less potent than in guinea pigs. The concentration of NO in exhaled air increased 3-fold when changing from in situ blood auto-perfusion of rabbit lungs to in situ perfusion with saline medium. Addition of L-N omega-nitro-arginine-methylester to the saline perfusion medium evoked a reduction of NO concentrations in the air from the ventilated perfused lungs. Perfusion of lungs with Ca(2+)-free medium induced significant decrements in NO concentrations in exhaled air, an effect partly reversed upon reintroducing Ca2+ into the medium. In conclusion, NO was detected in exhaled air from humans and animals by chemiluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)
Persson
M G
MG
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Midtvedt
T
T
Leone
A M
AM
Gustafsson
L E
LE
D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001944:Breath Tests; D002118:Calcium / Q000494:pharmacology*; D005260:Female; D005856:Germ-Free Life; D006168:Guinea Pigs; D006801:Humans; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium