Selective inhibition of basal but not agonist-stimulated activity of nitric oxide in rat aorta by NG-monomethyl-L-arginine.
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.
Frew
J D
JD
Department of Pharmacology, University of Glasgow.
Paisley
K
K
Martin
W
W
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D019323:omega-N-Methylarginine
D010656:Phenylephrine; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine