Stimulus-specific blockade of nitric oxide-mediated dilatation by asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) in rat aorta and carotid artery

被引:5
作者
AL-Zobaidy, Mohammed J. [1 ]
Craig, John [1 ]
Brown, Kirsty [1 ]
Pettifor, Graeme [1 ]
Martin, William [1 ]
机构
[1] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
关键词
ADMA; Endothelium; Nitric oxide; L-NMMA; NOS inhibitor; Vasodilatation; ENDOTHELIUM-DEPENDENT RELAXATION; BOVINE RETRACTOR PENIS; L-ARGININE; RELAXING FACTOR; DIFFERENTIAL SENSITIVITY; N(G)-SUBSTITUTED ANALOGS; ENDOGENOUS INHIBITOR; SYNTHASE INHIBITORS; SUPEROXIDE ANION; CORONARY-ARTERY;
D O I
10.1016/j.ejphar.2011.10.024
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu M) 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. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:78 / 84
页数:7
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