title: Involvement of the peroxisome proliferator-activated receptor (PPAR) alpha in vascular response of endocannabinoids in the bovine ophthalmic artery.
abstract: Endocannabinoids regulate vascular tone in a variety of vascular tissues. This study aimed to investigate the role of peroxisome proliferators-activated receptors (PPARs) in anandamide- and palmitoylethanolamide-induced relaxant responses on the bovine ophthalmic artery and to evaluate the mechanisms involved. The effects of anandamide and palmitoylethanolamide were examined under myographic conditions on arterial rings pharmacologically pre-contracted with 5-HT. Anandamide and palmitoylethanolamide relaxed the ophthalmic artery rings in time- and concentration-dependent manner stimulating the PPAR alpha (PPARα). The vasorelaxation to endocannabinoids was inhibited by PPARα antagonist GW6471 (1μM), but not the PPAR gamma (PPARγ) antagonist GW9662 (1 μM). Anandamide-induced relaxation was attenuate during the first 60 min by AM251, a selective antagonist of cannabinoid CB(1) receptors, and Pertussis toxin, an inhibitor of G(i/o) protein; by the contrast, the palmitoylethanolamide-induced vasorelaxation was unaffected by cannabinoid antagonists and Pertussis toxin. Endothelium removal decreases slightly the potency and efficacy to endocannabinoids. The relaxant effect to anandamide and palmitoylethanolamide was inhibited by L-NMMA (300 μM), an inhibitor of nitric oxide synthase, and iberiotoxin (200 nM), a selective blocker of large conductance Ca²⁺-activated K⁺ (BK(Ca)). These data support the view that anandamide and palmitoylethanolamide relax the ophthalmic artery in a time-dependent manner via the transcription factors PPARα suggesting a function for them in the physiological mechanisms of vascular regulation.
authors.affiliation: Department of Pharmacobiology, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Romano
authors.forename: Marcello Diego
authors.initials: MD
authors.lastname: Lograno
mesh_terms: D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002417:Cattle; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D009213:Myography; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009880:Ophthalmic Artery / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D047493:PPAR alpha; D047495:PPAR gamma; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D012701:Serotonin; C005958:palmidrol; D019001:Nitric Oxide Synthase; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C078814:anandamide