Conversion of inhaled nitric oxide to nitrate in man

Abstract

1 Nitric oxide (NO) is potentially useful as a selective vasodilator drug 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 present study was to assess quantitatively the importance of this pathway for inhaled NO in human subjects. 2 Healthy subjects inhaled ¹⁵NO (25 p.p.m.) for 1 h. The plasma and urine levels of ¹⁵NO₃- were followed for 2 and 48 h, respectively. 3 The measured retention of ¹⁵NO in the lungs was 224 ± 13 μmol, corresponding to 90 ± 2% of the inhaled amount. Plasma ¹⁵NO₃- increased during the inhalation of ¹⁵NO, to about 15μmoll^_1, and fell when inhalation of ¹⁵NO was terminated. 4 Urinary excretion of ¹⁵NO₃- during the first 24 h after inhalation was 154 ± 12μmol. During the following 24 h another 8 ± 2 μmol of ¹⁵NO₃ appeared in the urine. 5 We conclude that conversion of inhaled NO to nitrate is a major metabolic pathway in man, covering more than 70% of its inactivation. The metabolic fate of the remaining NO inhaled requires further study.