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l ‐N G ‐monomethyl arginine and l ‐N G ‐nitro arginine inhibit non‐adrenergic, non‐cholinergic relaxation of the mouse anococcygeus muscle
Author(s) -
Gibson A.,
Mirzazadeh Shokoufeh,
Hobbs A.J.,
Moore P.K.
Publication year - 1990
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 - 10.1111/j.1476-5381.1990.tb12976.x
Subject(s) - nitroarginine , omega n methylarginine , arginine , sodium nitroprusside , chemistry , nitric oxide , carbachol , endothelium derived relaxing factor , endocrinology , medicine , pharmacology , stimulation , biochemistry , biology , amino acid
1 The effects of l ‐N G ‐monomethyl arginine ( l ‐NMMA) and l ‐N G ‐nitro arginine ( l ‐NOARG) on non‐adrenergic, non‐cholinergic (NANC) relaxations of the mouse anococcygeus were investigated. 2 l ‐NMMA (10–200 μ m ) produced a concentration‐related inhibition of the NANC response; the inhibitory effect of 50 μ m l ‐NMMA was completely reversed by l ‐arginine but not d ‐arginine (both 100 μ m ). 3 l ‐NOARG (1–50 μ m ) also produced a concentration‐related inhibition of the NANC response and was some 30–50 times more potent than l ‐NMMA; again, the effects of 10 μ m l ‐NOARG were reversed by 100 μ m l ‐, but not d ‐, arginine. By itself 100 μ m l ‐arginine did not relax the tissue, but did cause a slight potentiation of the NANC response. 4 Sodium nitroprusside (0.01–10 μ m ), hydroxylamine (0.1–100 μ m ), sodium azide (1–100 μ m ) and nitric oxide (3–120 μ m ) all relaxed carbachol‐induced tone; relaxations to submaximal concentrations of these nitrovasodilators were unaffected by either 50 μ m l ‐NMMA or 10 μ m l ‐NOARG. 5 l ‐NOARG 10 μ m did not inhibit, but rather potentiated, contractions of the mouse anococcygeus due to stimulation of its sympathetic nerves. 6 The inhibitory effects of 10 μ m l ‐NOARG on NANC relaxations were reversed by l ‐arginine (by 131%), l ‐citrulline (by 75%), l ‐arginine methyl ester (by 46%) and l ‐homoarginine (by 22%), but were unaffected by a variety of other amino acids and their derivatives (all at 100 μ m ). 7 The results provide strong evidence that NANC relaxations of the mouse anococcygeus are mediated by an endogenous nitrate material, probably derived from l ‐arginine, and confirm that l ‐NOARG provides a very useful and potent drug for the investigation of endogenous nitrate function.