title: Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries.
abstract: OBJECTIVE
  The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans.
  
  
  METHODS
  Mesenteric arteries were obtained from patients receiving colorectal surgery and mounted on a myograph. Arteries were contracted and 2-AG concentration-response curves were carried out. Mechanisms of action were characterised pharmacologically. Post hoc analysis was carried out to assess the effects of cardiovascular disease/risk factors on 2-AG responses.
  
  
  RESULTS
  2-AG caused vasorelaxation of human mesenteric arteries, independent of cannabinoid receptor or transient receptor potential vanilloid-1 activation, the endothelium, nitric oxide or metabolism via monoacyglycerol lipase or fatty acid amide hydrolase. 2-AG-induced vasorelaxation was reduced in the presence of indomethacin and flurbiprofen, suggesting a role for cyclooxygenase metabolism 2-AG. Responses to 2-AG were also reduced in the presence of Cay10441, L-161982 and potentiated in the presence of AH6809, suggesting that metabolism of 2-AG produces both vasorelaxant and vasoconstrictor prostanoids. Finally, 2-AG-induced vasorelaxation was dependent on potassium efflux and the presence of extracellular calcium.
  
  
  CONCLUSIONS
  We have shown for the first time that 2-AG causes vasorelaxation of human mesenteric arteries. Vasorelaxation is dependent on COX metabolism, activation of prostanoid receptors (EP4 & IP) and ion channel modulation. 2-AG responses are blunted in patients with cardiovascular risk factors.
authors.affiliation: School of Medicine, University of Nottingham, Royal Derby Hospital, Derby DE22 3DT, United Kingdom. Electronic address: mbzso@nottingham.ac.uk.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stanley
authors.affiliation: School of Medicine, University of Nottingham, Royal Derby Hospital, Derby DE22 3DT, United Kingdom.
authors.forename: Saoirse E
authors.initials: SE
authors.lastname: O'Sullivan
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology*; D005480:Flurbiprofen / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D005989:Glycerides; D005480:Flurbiprofen; C094503:glyceryl 2-arachidonate; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D007213:Indomethacin
keywords: 2-Arachidonoylglycerol; Cyclooxygenase; Endocannabinoid; Human; Prostanoid; Vasorelaxation