CONVERSION OF INHALED NITRIC-OXIDE TO NITRATE IN MAN

1 Nitric oxide (NO) is potentially useful as a selective vasodilator d rug in infants and adults with pulmonary hypertension. In vitro and in vivo observations demonstrate that NO may be converted to nitrate in the blood, to be further excreted into the urine. The aim of the prese nt study was to assess quantitatively the importance of this pathway f or inhaled NO in human subjects. 2 Healthy subjects inhaled (NO)-N-15 (25 p.p.m.) for 1 h. The plasma and urine levels of (NO3)-N-15- were f ollowed for 2 and 48 h, respectively. 3 The measured retention of (NO) -N-15 in the lungs was 224 +/- 13 mu mol, corresponding to 90 +/- 2% o f the inhaled amount. Plasma (NO3)-N-15- increased during the inhalati on of (NO)-N-15, to about 15 mu mol l(-1), and fell when inhalation of (NO)-N-15 was terminated. 4 Urinary excretion of (NO3)-N-15- during t he first 24 h after inhalation was 154 +/- 12 mu mol. During the follo wing 24 h another 8 +/- 2 mu mol of (NO3)-N-15- appeared in the urine. 5 We conclude that conversion of inhaled NO to nitrate is a major met abolic pathway in man, covering more than 70% of its inactivation. The metabolic fate of the remaining NO inhaled requires further study.