Selective inhibition of basal but not agonist‐stimulated activity of nitric oxide in rat aorta by NG‐monomethyl‐l‐arginine

Open Access
Publisher Website
Google Scholar
Abstract
1 Two inhibitors of nitric oxide synthase, NG-monomethyl-l-arginine (l-NMMA, 1–100 μm) and NG-nitro-l-arginine (l-NOARG, 3–300 μm), 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 mm) 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 nm--3 μm) induced relaxations which were inhibited in a concentration-dependent manner by l-NOARG (10–100 μm). 3 In contrast to the action of l-NOARG, l-NMMA (100–1000 μm) had no effect on acetylcholine-induced relaxations. l-NMMA (100–300 μm) also had no effect on the endothelium-dependent relaxant actions of ATP (0.1–100 μm), whereas l-NOARG (100 μm) produced powerful blockade. 4 Unexpectedly, pretreatment with l-NMMA (30–300 μm), as with the endogenous substrate l-arginine (10 μm–10 mm), inhibited in a concentration-dependent manner the ability of l-NOARG (30 μm) 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.