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Selective inhibition of basal but not agonist‐stimulated activity of nitric oxide in rat aorta by N G ‐monomethyl‐ l ‐arginine
Author(s) -
Frew Joyce D.,
Paisley Karen,
Martin William
Publication year - 1993
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.1476-5381.1993.tb13913.x
Subject(s) - agonist , nitric oxide , arginine , aorta , basal (medicine) , chemistry , nitric oxide synthase , endocrinology , medicine , pharmacology , biophysics , biochemistry , receptor , biology , amino acid , insulin
1 Two inhibitors of nitric oxide synthase, N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA, 1–100 μ m ) and N G ‐nitro‐ l ‐arginine ( l ‐NOARG, 3–300 μ m ), each produced a concentration‐dependent augmentation of phenylephrine‐induced tone in endothelium‐containing but not endothelium‐denuded rings of rat aorta. Pretreatment with l ‐arginine (10 m m ) prevented the augmentation of tone induced by l ‐NOARG and l ‐NMMA. 2 Following induction of sub‐maximal tone with phenylephrine in endothelium‐containing rings, acetylcholine (1 n m‐ ‐3 μ m ) induced relaxations which were inhibited in a concentration‐dependent manner by l ‐NOARG (10–100 μ m ). 3 In contrast to the action of l ‐NOARG, l ‐NMMA (100–1000 μ m ) had no effect on acetylcholine‐induced relaxations. l ‐NMMA (100–300 μ m ) also had no effect on the endothelium‐dependent relaxant actions of ATP (0.1–100 μ m ), whereas l ‐NOARG (100 μ m ) produced powerful blockade. 4 Unexpectedly, pretreatment with l ‐NMMA (30–300 μ m ), as with the endogenous substrate l ‐arginine (10 μ m –10 m m ), inhibited in a concentration‐dependent manner the ability of l ‐NOARG (30 μ m ) to block acetylcholine‐induced relaxation. 5 The ability of l ‐NOARG to augment phenylephrine‐induced tone and inhibit relaxation by acetylcholine and ATP in endothelium‐containing rings is consistent with blockade of basal and agonist‐stimulated production of nitric oxide, respectively. 6 The ability of l ‐NMMA to augment phenylephrine‐induced tone without affecting relaxation to acetylcholine or ATP in endothelium‐containing rings suggests a selective ability to block basal but not agonist‐stimulated production of nitric oxide in rat aorta.