The ability of asymmetric dimethylarginine (ADMA) or monomethylarginine (L-NMMA) to block endothelium-dependent, nitric oxide-mediated relaxation in rat aorta is inversely related to the efficacy of the relaxant stimulus

Al-Zobaidy, M. J. and Martin, W. (2014) The ability of asymmetric dimethylarginine (ADMA) or monomethylarginine (L-NMMA) to block endothelium-dependent, nitric oxide-mediated relaxation in rat aorta is inversely related to the efficacy of the relaxant stimulus. European Journal of Pharmacology, 741, pp. 171-177. (doi: 10.1016/j.ejphar.2014.08.002)

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Abstract

Previous work on rat aorta has shown that L-NMMA and ADMA each enhance vasoconstrictor-induced tone, consistent with blockade of basal nitric oxide activity, whereas they exert little inhibitory effect on acetylcholine-induced relaxation when tone is matched carefully to that of control tissues. The aim of this study was to determine if the ability of L-NMMA or ADMA to inhibit nitric oxide-mediated relaxation was critically determined by the efficacy of the relaxant stimulus. The effects of L-NMMA or ADMA were examined on relaxation to a range of agonists producing different maximal responses, namely, acetylcholine, the muscarinic partial agonist, butyrylcholine, and calcitonin gene-related peptide-1 (CGRP-1). The effects of L-NMMA or ADMA were also examined on relaxation to acetylcholine when its apparent efficacy at the M3 muscarinic receptor was reduced using the irreversible receptor blocking agent, phenoxybenzamine. Maximal relaxation induced by butyrylcholine or CGRP-1 was lower than to acetylcholine. While acetylcholine-induced relaxation was largely resistant to blockade by L-NMMA or ADMA (0.1 or 1 mM), relaxation to butyrylcholine or CGRP-1 was powerfully suppressed. Phenoxybenzamine (0.1–10 μM for 30 min) concentration-dependently reduced maximal acetylcholine-induced relaxation. When the efficacy of acetylcholine was reduced by phenoxybenzamine, its residual relaxant effect was powerfully inhibited by L-NMMA or ADMA (0.1 or 1 mM). Thus, in rat aorta, the ability of L-NMMA or ADMA to block agonist-induced nitric oxide activity is critically determined by the efficacy of the relaxant stimulus.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Martin, Professor William
Authors: Al-Zobaidy, M. J., and Martin, W.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:European Journal of Pharmacology
Publisher:Elsevier B.V.
ISSN:0014-2999
ISSN (Online):1879-0712

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