CA2-DEPENDENT AND CA2+-INDEPENDENT EXHALED NITRIC-OXIDE, PRESENCE IN GERM-FREE ANIMALS, AND INHIBITION BY ARGININE ANALOGS()

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.