Mg. Persson et al., CA2-DEPENDENT AND CA2+-INDEPENDENT EXHALED NITRIC-OXIDE, PRESENCE IN GERM-FREE ANIMALS, AND INHIBITION BY ARGININE ANALOGS(), European journal of pharmacology, 264(1), 1994, pp. 13-20
Nitric oxide (NO) was detected by chemiluminescence in exhaled air fro
m awake humans, anaesthetized rabbits, guinea pigs, germ-free rats and
conventional rats. Rabbits exhibited the highest concentrations, foll
owed by guinea pigs, humans and rats. There was no significant differe
nce between germ-free rats and control rats. The authenticity of NO wa
s confirmed in cold-trap experiments. Intravenous administration of in
hibitors of NO synthase (0.01-300 mg kg(-1)) to guinea pigs dose depen
dently reduced NO concentrations in exhaled air with the following pot
ency order: L-N-omega-nitro-arginine-methylester > asymmetric N-G,N-G-
dimethyl-L-arginine-dihydrochloride = L-N-G-mono-methyl -arginine = L-
N-5-(1-iminoethyl)-ornithine = aminoguanidine > L-canavanine. The effe
ct of the NO synthase inhibitors was partly or fully reversed by L-arg
inine (1 g kg(-1) i.v.), and L-arginine per se induced a significant i
ncrement of NO in exhaled air. In rats, L-N-omega-nitro-arginine-methy
lester was considerably less potent than in guinea pigs. The concentra
tion 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 f
rom the ventilated perfused lungs. Perfusion of lungs with Ca2+-free m
edium induced significant decrements in NO concentrations in exhaled a
ir, an effect partly reversed upon reintroducing Ca2+ into the medium.
In conclusion, NO was detected in exhaled air from humans and animals
by chemiluminescence. Nitric oxide in exhaled air originates from the
respiratory system and is formed from L-arginine in a Ca2+-dependent
manner. Microbial activity is not necessary for formation of NO in the
respiratory system.