Distribution and metabolism of NG-nitro-L-arginine and NG-nitro-L-arginine methylester in canine blood in vitro.

The aim of the present study was to investigate the metabolism of the two NO-synthase inhibitors NG-nitro-L-arginine (L-NA) and NG-nitro-L-arginine methylester (L-NAME) in canine blood in vitro. Blood and plasma samples were incubated with L-NAME or L-NA respectively and the drug levels were determined in blood, plasma and blood cells by means of high performance liquid chromatography. Incubation of blood or plasma with L-NAME revealed that L-NAME is metabolized to L-NA in blood and plasma. After plasma incubation with L-NA, the L-NA levels remain stable over the whole observation period; in agreement with the data in plasma the whole amount of L-NA added to blood was detectable in blood after 4 h of incubation suggesting that L-NA undergoes no further metabolism. Drug concentrations determined in blood cells after 4 h of blood incubation with L-NAME or L-NA revealed that L-NAME easily enters the blood cells, whereas only a small portion of L-NA is found in the blood cells 4 h after blood incubation with L-NA. In conclusion, the present study demonstrates that L-NAME is metabolized to L-NA in canine blood and plasma in vitro. The fact that L-NAME but nearly no L-NA enters the cellular blood compartment led us to the assumption that although L-NA is an active metabolite of L-NAME, NO synthase may be differently inhibited by L-NA and L-NAME due to their different distribution characteristics.