Conversion of inhaled nitric oxide to nitrate in man

Abstract

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. 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. 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. 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. 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. 1995 British Pharmacological Society