THE L-ARGININE-NITRIC OXIDE PATHWAY IS THE MAJOR SOURCE OF PLASMA NITRITE IN FASTED HUMANS

N-15 guanidino-labelled L-arginine was infused into fasted human volun teers giving, at equilibrium, a stable 1:10 ratio of N-15 to N-14 argi nine in the plasma. Separate GC-MS assays were used to compare the deg ree of enrichment of plasma arginine, nitrite and nitrate and thus def ine the quantitative relationship between the L-arginine:nitric oxide (NO) pathway and the formation of these oxides of nitrogen. N-15 nitri te enrichments rose to 8.3% (SD 0.5), five hours after the start of th e infusion. In contrast, N-15 nitrate enrichments apparently rose to o nly 1.6% (SD 0.4) at this time. This discrepancy could be explained by our finding that the commonly used Tesch GC-MS nitrate assay is subje ct to considerable interference from non-nitrate sources in plasma. Ta king this into account, nitrate enrichments were similar to those obse rved for plasma nitrite. These results therefore indicate that the mea surement of these compounds in plasma is a valid indicator of NO gener ation in fasted humans. (C) 1995 Academic Press, Inc.