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

Abstract

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