title: Dietary n-3 polyunsaturated fatty acids and endothelium dysfunction induced by lysophosphatidylcholine in Syrian hamster aorta.
abstract: This study investigated the influence of an eicosapentaenoic acid (EPA)- or a docosahexaenoic acid (DHA)-supplemented diet on the deleterious effects of lysophosphatidylcholine (LPC) on endothelium-dependent vasorelaxation of Golden Syrian hamster thoracic aorta. In a second step, LPC-modulated phospholipase A(2) (PLA(2))-derived ways of relaxation were investigated. Golden Syrian hamsters were fed for 6 weeks with a control diet or an EPA- or DHA-supplemented diet. Aortic fatty acid composition was analyzed by gas chromatography. Aortic rings were incubated for 20 minutes with LPC before constructing cumulative concentration-response curves for acetylcholine (ACh; 3 nmol/L-30 micromol/L) or sodium nitroprusside (3 nmol/L-30 micromol/L). The EPA- or DHA-supplemented diet increased n-3 polyunsaturated fatty acids in aortic fatty acids content because of the increase of EPA or DHA content, respectively, and decreased arachidonic acid aortic content. Lysophosphatidylcholine (1, 10, 15, and 20 micromol/L) induced a concentration-dependent inhibition of ACh-induced relaxation of preconstricted aortic rings in the control group, but did not influence sodium nitroprusside-induced aortic relaxation. The DHA- or EPA-supplemented diet worsened LPC (20 micromol/L) inhibitory effects on ACh-induced vasorelaxation. In the control diet group, ACh-induced relaxation was abolished by the nitric oxide synthase inhibitor (l-N(G)-nitro-arginine methyl ester; 100 micromol/L), whether LPC was added or not. The ACh-induced vasorelaxation was partially inhibited by PLA(2) inhibitors methyl arachidonyl fluorophosphonate (25 micromol/L) and arachidonyl trifluoromethyl ketone (20 micromol/L) as well as by the combination of 2 Ca(2+)-dependent potassium (K(Ca)) channel inhibitors charybdotoxin (0.1 micromol/L) plus apamin (0.3 micromol/L). In the presence of LPC (20 micromol/L), ACh-induced vasorelaxation was abolished by these inhibitors. These effects were not influenced by DHA or EPA diet. Our results suggested that EPA- or DHA-supplemented diet did not exhibit any beneficial effect against LPC-induced inhibition of endothelium-dependent aortic relaxation in Golden Syrian hamsters. These LPC effects were associated in our study not only with an inhibition of nitric oxide-dependent vasorelaxation, but also with a concomitant activation of a compensatory vasorelaxant pathway depending both on PLA(2) metabolites and on K(Ca) channel opening.
authors.affiliation: INRA-UMR-1154, Châtenay-Malabry F-92296, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucas
authors.forename: Alain
authors.initials: A
authors.lastname: Grynberg
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
authors.forename: Françoise
authors.initials: F
authors.lastname: Goirand
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D006224:Cricetinae; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000008:administration & dosage*; D008647:Mesocricetus; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011897:Random Allocation
chemical_list: D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; D008244:Lysophosphatidylcholines; D064801:Phospholipase A2 Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D054467:Phospholipases A2; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester