title: Hydrogen peroxide as a mediator of vasorelaxation evoked by N-oleoylethanolamine and anandamide in rat small mesenteric arteries.
abstract: Hydrogen 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.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Wheal
authors.forename: Stephen P H
authors.initials: SP
authors.lastname: Alexander
authors.forename: Michael D
authors.initials: MD
authors.lastname: Randall
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D063388:Endocannabinoids; D004983:Ethanolamines / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; C033595:N-oleoylethanolamine; D002217:Carbachol; D006861:Hydrogen Peroxide; D002374:Catalase; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester