Splanchnic metabolism of dietary arginine in relation to nitric oxide synthesis in normal adult man

Urinary nitrate (NO₃) is the stable end product of nitric oxide, which is formed, in turn, from a guanidino nitrogen of arginine. We have conducted two experiments, each in four healthy adult men receiving a low nitrate diet for 7-10 days, to investigate the in vivo conversion of arginine to nitrate. In the first study [guanidino-¹⁵N₂, 5,5-²H₂]arginine was given on day 7 via a primed continuous intravenous infusion for 8 h. In the second study, the labeled arginine was given for 8 h by the intragastric route on day 7 and by the intravenous route on day 10. Measurement of ¹⁵NO₃ output in urine collected for 24 h beginning at the time of the arginine tracer infusion revealed a more extensive transfer of ¹⁵N when the arginine tracer was given intragastricly. From the comparative labeling of ¹⁵NO₃ after administration of the tracer arginine via the intragastric and intravenous routes, we estimate that 16% ± 2% of the daily production of nitrate arises from the metabolism of dietary arginine that is taken up during its "first pass" in the splanchnic region. Hence, nitric oxide production occurs, to a measurable extent, in this area in healthy subjects, raising the question as to how various pathophysiological states might alter the relations between exogenous and endogenous sources of arginine as precursors of NO· and the relative contributions made by various organs to whole body (NO·) NO₃ formation. These results also raise important questions about the use of nitric oxide synthase inhibitors in animal and human studies.