title: Distribution and metabolism of NG-nitro-L-arginine and NG-nitro-L-arginine methylester in canine blood in vitro.
abstract: 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.
authors.affiliation: Department of Cardiovascular Pharmacology, University of Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Krejcy
authors.forename: S
authors.initials: S
authors.lastname: Schwarzacher
authors.forename: G
authors.initials: G
authors.lastname: Raberger
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D004285:Dogs; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine
chemical_list: D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester