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Scavenging of hydroxyl radicals but not of peroxynitrite by inhibitors and substrates of nitric oxide synthases
Author(s) -
Rehman Almas,
Whiteman Matthew,
Halliwell Barry
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701556
Subject(s) - peroxynitrite , chemistry , nitric oxide , nitration , radical , arginine , scavenger , reactive nitrogen species , hydroxyl radical , biochemistry , peroxynitrous acid , reactive oxygen species , nitric oxide synthase , mannitol , superoxide , organic chemistry , enzyme , amino acid
1 The nitric oxide synthase inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) is widely used to study the role of NO • in physiological and pathological processes, including its role in the generation of the cytotoxic species peroxynitrite (ONOO − ) and of reactive oxygen radicals such as hydroxyl (OH • ). Often l ‐NAME is applied to tissues at mM concentrations. At such high concentrations, it might act as a free radical scavenger. A similar possibility might apply to the use of high levels of arginine to study the role of NO . in atherogenesis. 2 We therefore examined the rate of scavenging of OH • by l ‐NAME and found that l ‐NAME reacts more quickly with OH . than the established ‘OH . scavenger’ mannitol and the widely used ‘OH • trap’ salicylate. However, d ‐NAME can scavenge OH • at rates equal to l ‐NAME. Both l ‐ and d ‐arginine were also good OH • scavengers, comparable in effectiveness to mannitol. 3 Neither l ‐NAME, d ‐NAME, l ‐arginine nor d ‐arginine was able to inhibit ONOO − ‐dependent nitration of tyrosine, suggesting that they are unlikely to be scavengers of ONOO − ‐derived nitrating species. 4 Neither l ‐NAME, d ‐NAME, l ‐arginine nor d ‐arginine was able to inhibit the inactivation of α 1 ‐antiproteinase by ONOO − , suggesting that they cannot prevent direct oxidations by peroxynitrite. 5 We conclude that l ‐NAME has sufficient activity as an OH • scavenger to confound certain pharmacological experiments. However, this explanation of its biological effects can be ruled out if control experiments show that d ‐NAME has no effect and that l ‐arginine (also a free radical scavenger) antagonizes the action of l ‐NAME.