title: Stimulus-specific blockade of nitric oxide-mediated dilatation by asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) in rat aorta and carotid artery.
abstract: Previous work on female rat aorta has shown that although monomethylarginine (L-NMMA) and asymmetric dimethylarginine (ADMA) each enhance submaximal phenylephrine-induced tone, consistent with blockade of basal nitric oxide activity, neither agent has any major effect on acetylcholine-induced relaxation. The aim of this study was to adopt a variety of different experimental approaches to test the hypothesis that these methylarginines block basal but not agonist-stimulated activity of nitric oxide. Basal activity of nitric oxide was assessed by observing the rise in submaximal phenylephrine-induced tone produced by nitric oxide synthase (NOS) inhibitors in male and female aorta and female carotid artery, and by monitoring the vasodilator actions of superoxide dismutase (SOD) or the PDE 5 inhibitor, T-0156. Agonist-stimulated activity of nitric oxide was assessed by observing the relaxant actions of acetylcholine or calcium ionophore A23187. L-NMMA, ADMA and L-NAME (100 μM) each enhanced submaximal phenylephrine-induced tone and inhibited SOD- or T-0156-induced relaxation, consistent with each NOS inhibitor blocking basal nitric oxide activity. In contrast, L-NMMA and ADMA had little effect on acetylcholine- or A23187-induced relaxation, while L-NAME produced powerful blockade. These observations provide support for the hypothesis that L-NMMA and ADMA selectively block basal over agonist-stimulated activity of nitric oxide in rat vessels.
authors: College of Medical, Veterinary and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
authors: Mohammed J
authors: MJ
authors: Al-Zobaidy
authors: John
authors: J
authors: Craig
authors: Kirsty
authors: K
authors: Brown
authors: Graeme
authors: G
authors: Pettifor
authors: William
authors: W
authors: Martin
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D009287:Naphthyridines; D011743:Pyrimidines; C473961:T0156; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester