title: Effect of dietary docosahexaenoic acid on the endothelium-dependent vasorelaxation in diabetic rats.
abstract: 1. The aim of the present study was to investigate the responses to acetylcholine (ACh; 3 nmol/L-30 micromol/L) and sodium nitroprusside (SNP; 3 nmol/L-30 micromol/L) of precontracted aortic rings from diabetic rats supplemented with docosahexaenoic acid (DHA). 2. Diabetes was induced by streptozotocin (STZ; 55 mg/kg). Diabetic and sham rats were fed, over a period of 8 weeks, either control diet or a DHA-supplemented diet. Aortic endothelial fatty acid composition was analysed by gas chromatography. The involvement of endothelial-derived nitric oxide (NO) and cyclo-oxygenase (COX) metabolites in response to ACh was assessed using the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (100 micromol/L) and the COX inhibitor indomethacin (1 micromol/L), respectively. 3. The DHA-supplemented diet induced a small increase in n-3 polyunsaturated fatty acids (PUFA; P < 0.001) owing to the incorporation of DHA in the endothelial cells of sham animals (1.6 +/- 0.2% in the DHA group compared with traces in the control group; P < 0.001) and diabetic animals (1.3 +/- 0.2% in the DHA group compared with traces in control group; P < 0.001), without a decrease in n-6 PUFA, despite a small decrease in arachidonic acid content (P < 0.05). Diabetes did not modify the incorporation of DHA in endothelial cells, but did significantly increase the arachidonic acid content (0.6 +/- 0.0 vs 0.4 +/- 0.1% in control group in the STZ and sham groups, respectively; P < 0.001). Acetylcholine-induced relaxation was significantly reduced in STZ groups compared with the sham groups (P < 0.001) and the DHA-supplemented diet did not modify these effects. In contrast, neither the DHA-supplemented diet nor diabetes affected the aortic relaxation induced by SNP. N(G)-Nitro-L-arginine methyl ester strongly inhibited the relaxant effects of ACh in the sham groups (P < 0.001) and abolished ACh-induced relaxation in the STZ groups (P < 0.001). The diet did not modify these effects. In the presence of indomethacin, the relaxation induced by ACh was decreased in the sham groups (P < 0.01), but not in the STZ groups. The DHA-supplemented diet did not have any effect on these responses. 4. In conclusion, these results suggest that, in the present study, the endothelial dysfunction occurring in the rat model of STZ-induced diabetes is associated with modifications of both the synthesis of COX derivatives and NO metabolism and is not affected by dietary supplementation with DHA.
authors.affiliation: UMR1154, INRA-Université Paris XI, Faculté de Pharmacie, Châtenay-Malabry, France. francoise.goirand@cep.u-psud.fr
authors.forename: Françoise
authors.initials: F
authors.lastname: Goirand
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ovide-Bordeaux
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Renaud
authors.forename: Alain
authors.initials: A
authors.lastname: Grynberg
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D016718:Arachidonic Acid / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000503:physiopathology; D004032:Diet; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D009569:Nitric Oxide; D000109:Acetylcholine