Exhaled nitric oxide does not provide a marker of vascular endothelial function in healthy humans

In the lung, nitric oxide synthase (NOS) has been found in both alveolar ep ithelial and vascular endothelial cells. Nitric oxide (NO) in the exhaled a ir stemming from the lower respiratory tract has been claimed to represent a marker of the vascular endothelial NO production. Experimental evidence f or this concept, however, is lacking. We compared, in eight healthy volunte ers, effects on exhaled NO of epithelial NOS inhibition by N-G-monomethyl-L -arginine (L-NMMA) inhalation (6 mg/kg over 15 min) with those of endotheli al NOS inhibition by L-NMMA infusion (25 mu g/kg/min for 30 min). We also m easured blood pressure, heart rate, and L-NMMA plasma concentration. The ma jor new findings were that L-NMMA inhalation which did not have any detecta ble effect on hemodynamics and L-NMMA plasma concentration, decreased the p ulmonary exhaled NO by almost 40%. In contrast, L-NMMA infusion that inhibi ted endothelial NOS, as evidenced by an increase in blood pressure and a de crease in heart rate, had only a barely detectable effect on exhaled NO (-1 1 +/- 4% from baseline). Pulmonary exhaled NO is mostly of epithelial rathe r than endothelial origin, and does not provide a marker for vascular endot helial NO production and/or endothelial function in healthy humans.