title: Vascular metabolism of anandamide to arachidonic acid affects myogenic constriction in response to intraluminal pressure elevation.
abstract: OBJECTIVE
  We hypothesized that arachidonic acid produced by anandamide breakdown contributes to the vascular effects of anandamide.
  
  
  METHODS
  Isolated, pressurized rat skeletal muscle arteries, which possess spontaneous myogenic tone, were treated with anandamide, arachidonic acid, capsaicin (vanilloid receptor agonist), WIN 55-212-2 (cannabinoid receptor agonist), URB-597 (FAAH inhibitor), baicalein (lipoxygenase inhibitor), PPOH (cytochrome P450 inhibitor), and indomethacin (cyclooxygenase inhibitor). Changes in the arteriolar diameter in response to the various treatments were measured. To assess the effect of anandamide metabolism, anandamide was applied for 20 min followed by washout for 40 min. This protocol was used to eliminate other, more direct effects of anandamide in order to reveal how anandamide metabolism may influence vasodilation.
  
  
  RESULTS
  Anandamide at a low dose (1μM) evoked a loss of myogenic tone, while a high dose (30 μM) not only attenuated the myogenic response but also evoked acute dilation. Both of these effects were inhibited by the FAAH inhibitor URB-597 and were mimicked by arachidonic acid. The CB1 and CB2 agonist R-WIN 55-212-2 and the vanilloid receptor agonist capsaicin were without effect on the myogenic response. The inhibition of the myogenic response by anandamide was blocked by indomethacin and PPOH, but not by baicalein or removal of the endothelium. FAAH expression in the smooth muscle cells of the blood vessels was confirmed by immunohistochemistry.
  
  
  CONCLUSIONS
  Anandamide activates the arachidonic acid pathway in the microvasculature, affecting vascular autoregulation (myogenic response) and local perfusion.
authors.affiliation: Institute of Cardiology, Division of Clinical Physiology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Czikora
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Lizanecz
authors.forename: Judit
authors.initials: J
authors.lastname: Boczán
authors.forename: Andrea
authors.initials: A
authors.lastname: Daragó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.forename: István
authors.initials: I
authors.lastname: Édes
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001549:Benzamides; D048588:Benzoxazines; D001794:Blood Pressure / Q000502:physiology*; D002208:Caproates; D002211:Capsaicin; D002219:Carbamates; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D044950:Flavanones; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007213:Indomethacin; D009025:Morpholines; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
chemical_list: C121755:6-(2-propargyloxyphenyl)hexanoic acid; D001095:Arachidonic Acids; D001549:Benzamides; D048588:Benzoxazines; D002208:Caproates; D002219:Carbamates; D063388:Endocannabinoids; D044950:Flavanones; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C006680:baicalein; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D002211:Capsaicin; C078814:anandamide; D007213:Indomethacin