METABOLISM AND EXCRETION OF NITRIC-OXIDE IN HUMANS - AN EXPERIMENTAL AND CLINICAL-STUDY

Despite the increasing insight in the clinical importance of nitric ox ide (NO), formerly known as endothelium-derived relaxing factor (EDRF) , there is limited information about the metabolism and elimination of this mediator in humans. We studied the degradation of NO in healthy subjects inhaling 25 ppm for 60 minutes and in patients with severe he art failure inhaling 20, 40, and 80 ppm in consecutive 10-minute perio ds. In other healthy subjects, the renal clearance of NO metabolite wa s measured. The metabolism ex vivo was evaluated by direct incubation of nitrite, the NO oxidation product, in blood from healthy humans. Du ring inhalation of NO, the plasma levels of nitrate increased progress ively, both in the healthy subjects (from 26 to 38 mumol/L, P<.001) an d in the patients (from 72 to 90 mumol/L, P<.001). Methemoglobin (MetH b) also increased in the healthy subjects (from 7 to 13 mumol/L, P<.00 1) as well as in the patients (from 19 to 42 mumol/L, P<.01). No chang e in nitrosohemoglobin (HbNO) was detected, either in the healthy subj ects or in the patients. In arterialized blood (02 saturation, 94% to 99%), incubated nitrite was semiquantitatively converted to nitrate an d MetHb. In venous blood (02 saturation, 36% to 85%) moderate amounts of HbNO were also formed. Plasma and urinary clearance of nitrate in h ealthy subjects averaged 20 mL/min. We conclude that uptake into the r ed blood cells with subsequent conversion to nitrate and MetHb is a ma jor metabolic pathway for endogenously formed NO. Nitrate may then ent er the plasma to be eliminated via the kidneys. The occurrence of HbNO in vivo probably indicates liberation of NO to partly deoxygenated bl ood.