title: The effects of oxidation products of arachidonic acid and n3 fatty acids on vascular and platelet function.
abstract: 15-F₂(t)-isoprostane (15-F₂(t)-IsoP), an oxidation product of arachidonic acid (AA), affects vascular and platelet function; however, the bioactivity of other fatty acids oxidation products is unknown. This paper studied rat aortic vascular reactivity and human platelet aggregation in response to 14 oxidation products of AA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and α-linolenic acid (ALA) compared with 15-F₂(t)-IsoP. It also compared the F₂(t)-IsoPs profile in human platelets. EPA-derived 15-F₃(t)-IsoP constricted rat aorta less than 15-F₂(t)-IsoP, but none of the other oxidation products affected vascular reactivity. Only 15-F₂(t)-IsoP (10⁻⁴ M) directly affected platelet aggregation. 15-F₃(t)-IsoP, ent-16-F₁-phytoprostane (from ALA) and isofurans A and B (from AA) inhibited reversible aggregation to U46619. Unlike plasma, the platelet profile of F₂-IsoP showed that 8-F(2t)-IsoP were higher than 15-F₂(t)-IsoP. Unlike 15-F₂(t)-IsoP, the test compounds derived from fatty acids oxidation did not affect vascular or platelet function. Elevated platelet 8-F₂(t)-IsoP could limit 15-F₂(t)-IsoP-induced aggregation under conditions of oxidant stress.
authors.affiliation: Cardiovascular Research Center, School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Western Australia, Australia. barden@uwa.edu.au
authors.forename: Anne
authors.initials: A
authors.lastname: Barden
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.forename: Peter
authors.initials: P
authors.lastname: Henry
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D016718:Arachidonic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D055815:Young Adult; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D003517:Cyclopentanes; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; C486066:phytoprostane F1; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015118:Eicosapentaenoic Acid