title: Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.
abstract: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor (AHR) expression was measured. TCDD significantly increased AA-mediated vasoconstriction on a chow diet by increasing the contribution of P450s and TP receptor to the constriction response. In contrast, the n-3 PUFA diet prevented the TCDD-induced increase in AA vasoconstriction and normalized the contribution of P450s and TP receptor. Although TCDD increased the levels of AA vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3 PUFA-derived vasodilators and TCDD increased these levels further. Interestingly, the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a significant effect on AHR expression. These data suggest that n-3 PUFAs can prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors, increasing vasodilators, and attenuating CYP1A1 induction, which has been shown previously to contribute to TCDD-induced vascular dysfunction.
authors: *Department of Pharmaceutical Sciences, University of New Mexico, New Mexico, 87131.
authors: Elani F
authors: EF
authors: Wiest
authors: *Department of Pharmaceutical Sciences, University of New Mexico, New Mexico, 87131.
authors: Mary T
authors: MT
authors: Walsh-Wilcox
authors: Lipidomix GmbH, Berlin, Germany.
authors: Michael
authors: M
authors: Rothe
authors: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Wolf-Hagen
authors: WH
authors: Schunck
authors: *Department of Pharmaceutical Sciences, University of New Mexico, New Mexico, 87131 mwalker@salud.unm.edu.
authors: Mary K
authors: MK
authors: Walker
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D015525:Fatty Acids, Omega-3; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; 20-HETE; arachidonic acid; aryl hydrocarbon receptor; cytochrome P4501A1; omega-3 polyunsaturated fatty acids; vasoconstriction