Amanda J Wheal, Stephen P H Alexander, Michael D Randall
Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
European journal of pharmacology 2012 Jan 15Hydrogen peroxide (H(2)O(2)) has been shown to participate in endothelium-derived hyperpolarising factor (EDHF)-mediated mechanisms. Vasorelaxation to the endocannabinoid-like N-oleoylethanolamine (OEA) and anandamide has been shown to be endothelium-dependent. Therefore, the principal aim was to investigate whether H(2)O(2) plays a role in vasorelaxation to endocannabinoids in rat mesenteric arteries. We have also investigated the effects of catalase on endothelium-dependent relaxations and vascular responses to H(2)O(2). First- (G1) and third- (G3) order branches of the superior mesenteric artery from male, Wistar rats were mounted in a wire myograph, contracted with methoxamine, and concentration-response curves to anandamide, OEA carbachol or H(2)O(2), were constructed. The influence of nitric oxide production and H(2)O(2) breakdown on these responses were then investigated using L-NAME (300 μM), and catalase (1000 Uml(-1)) respectively. In G1 mesenteric arteries, vasorelaxations to carbachol and H(2)O(2) were inhibited by L-NAME, but not by catalase. Responses to both anandamide and OEA were also unaffected by catalase. In G3 mesenteric arteries, endothelium-dependent relaxations to carbachol were modestly affected by L-NAME, unaffected by catalase alone, but their combination greatly inhibited vasorelaxation. Similarly, catalase inhibited vasorelaxation to anandamide and OEA, and combined treatment with L-NAME further reduced this response. In G1 mesenteric arteries, vasorelaxation to H(2)O(2) is predominantly mediated by nitric oxide. We conclude that in G3 arteries H(2)O(2) activity contributes towards EDHF-type responses and vasorelaxation to endocannabinoids, either directly or indirectly. Given the association between vascular pathophysiology and H(2)O(2), these findings may provide a mechanism whereby disease states may influence responses to endocannabinoid and related mediators. Copyright © 2011 Elsevier B.V. All rights reserved.
Amanda J Wheal, Stephen P H Alexander, Michael D Randall. Hydrogen peroxide as a mediator of vasorelaxation evoked by N-oleoylethanolamine and anandamide in rat small mesenteric arteries. European journal of pharmacology. 2012 Jan 15;674(2-3):384-90
PMID: 22154756
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