Differential sensitivity of basal and acetylcholine-induced activity of nitric oxide to blockade by asymmetric dimethylarginine (ADMA) in the rat aorta

AL-Zobaidy, M.J., Craig, J. and Martin, W. (2010) Differential sensitivity of basal and acetylcholine-induced activity of nitric oxide to blockade by asymmetric dimethylarginine (ADMA) in the rat aorta. British Journal of Pharmacology, 160(6), pp. 1476-1483. (doi:10.1111/j.1476-5381.2010.00802.x)

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Background and purpose: Previous work has shown that NG-monomethyl-l-arginine (l-NMMA) paradoxically inhibits basal, but not ACh-stimulated activity of nitric oxide in rat aorta. The aim of this study was to determine if the endogenously produced agent, asymmetric NG, NG-dimethyl-l-arginine (ADMA), also exhibits this unusual selective blocking action. Experimental approach: The effect of ADMA on basal nitric oxide activity was assessed by examining its ability to enhance phenylephrine (PE)-induced tone in endothelium-containing rings. Its effect on ACh-induced relaxation was assessed both in conditions where ADMA greatly enhanced PE tone and where tone was carefully matched with control tissues at a range of different levels. Key results: ADMA (100 µM) potentiated PE-induced contraction, consistent with inhibition of basal nitric oxide activity. Higher concentrations (300–1000 µM) had no greater effect. Although ADMA (100 µM) also appeared to block ACh-induced relaxation when it enhanced PE tone to maximal levels, virtually no block was seen at intermediate levels of tone in the presence of ADMA. Even ADMA at 1000 µM had no effect on the maximal relaxation to ACh, although it produced a small (two- to threefold) reduction in sensitivity. ADMA and l-NMMA, like l-arginine (all at 1000 µM), protected ACh-induced relaxation against blockade by l-NAME (30 µM). Conclusions and implications: In the rat aorta, ADMA, like l-NMMA, blocks basal activity of nitric oxide, but has little effect on that stimulated by ACh. Further studies are required to explain these seemingly anomalous actions of ADMA and l-NMMA.

Item Type:Articles
Additional Information:The definitive version is available at www3.interscience.wiley.com
Keywords:ACh, ADMA, asymmetric dimethylarginine, endothelium, nitric oxide, NOS inhibitor, SDMA, symmetric dimethylarginine, vasodilatation
Glasgow Author(s) Enlighten ID:Martin, Professor William
Authors: AL-Zobaidy, M.J., Craig, J., and Martin, W.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:British Journal of Pharmacology
ISSN (Online):1476-5381
Published Online:14 April 2010
Copyright Holders:Copyright © 2010 Wiley-Blackwell
First Published:First published in British Journal of Pharmacology 160(6):1476-1483
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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