title: Omega-3 Polyunsaturated Fatty Acids Protect Against Cigarette Smoke-Induced Oxidative Stress and Vascular Dysfunction.
abstract: In cigarette smokers endothelial dysfunction, measured by flow-mediated dilation (FMD), precedes cardiovascular disease (CVD) and can be improved by supplementation with n - 3 polyunsaturated fatty acids (PUFAs). We developed a mouse model of cigarette smoke (CS)-induced endothelial dysfunction that resembles impaired FMD observed in human cigarette smokers and investigated the mechanism by which n - 3 PUFAs mediate vasoprotection. We hypothesized that loss of nitric oxide (NO)-dependent vasodilation in CS-exposed mice would be prevented by dietary n - 3 PUFAs via a decrease in oxidative stress. C57BL/6 mice were fed a chow or n - 3 PUFA diet for 8 weeks and then exposed to mainstream CS or filtered air for 5 days, 2 h/day. Mesenteric arterioles were preconstricted with U46619 and dilated by stepwise increases in pressure (0-40 mmHg), resulting in increases in flow, ± inhibitor of NO production or antioxidant, Tempol. Markers of oxidative stress were measured in lung and heart. CS-exposed mice on a chow diet had impaired FMD, resulting from loss of NO-dependent dilation, compared with air exposed mice. Tempol restored FMD by normalizing NO-dependent dilation and increasing NO-independent dilation. CS-exposed mice on the n - 3 PUFA diet had normal FMD, resulting from a significant increase in NO-independent dilation, compared with CS-exposed mice on a chow diet. Furthermore, n - 3 PUFAs decreased two CS-induced markers of oxidative stress, 8-epiprostaglandin-F2α levels and heme oxygenase-1 mRNA, and significantly attenuated CS-induced cytochrome P4501A1 mRNA expression. These data demonstrate that dietary n - 3 PUFAs can protect against CS-induced vascular dysfunction via multiple mechanisms, including increasing NO-independent vasodilation and decreasing oxidative stress.
authors.affiliation: Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico 87131.
authors.forename: Elani F
authors.initials: EF
authors.lastname: Wiest
authors.affiliation: Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico 87131.
authors.forename: Mary T
authors.initials: MT
authors.lastname: Walsh-Wilcox
authors.affiliation: Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico 87131.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Walker
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001273:Atmosphere Exposure Chambers; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D002317:Cardiovascular Agents / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000073865:Cigarette Smoking / Q000009:adverse effects*; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D012906:Smoke / Q000009:adverse effects; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002317:Cardiovascular Agents; D015525:Fatty Acids, Omega-3; D012906:Smoke
keywords: cigarette smoke; flow-mediated dilation; omega-3 polyunsaturated fatty acids; oxidative stress; vasodilation.