title: Decreased vascular H2S production is associated with vascular oxidative stress in rats fed a high-fat western diet.
abstract: A Western-style high-fat diet is known to cause vascular dysfunction and oxidative stress. H2S contributes to the regulation of vascular function and acts as a vasoprotective molecule; however, the effects of high-fat diet on vascular H2S production and function are not known. The aim of this study was to investigate the effects of high-fat diet on vascular function and H2S production. Wistar hooded rats were fed a western diet (WD, 21 % fat) or control rat chow (6 % fat) for 12 weeks. At the end of the experiment, the aorta was collected for assessing vascular function and NO and H2S bioavailability. Superoxide anion production was quantitated by lucigenin-enhanced chemiluminescence. The expression of NADPH oxidase subunit Nox2 and the H2S-producing protein cystathionine-γ-lyase (CSE) were examined by Western blotting. WD rats had significantly higher body weight and body fat than control (p < 0.001). Endothelial function and NO bioavailability were significantly reduced in the WD group (p < 0.05), but vascular smooth muscle cell function was unaffected. Vascular superoxide production and Nox2 expression were significantly increased in the aorta from WD rats. L-Cysteine-induced vasorelaxation was reduced in the WD group (p < 0.05) and insensitive to the inhibition of the CSE. In addition, vascular H2S bioavailability and CSE expression were significantly reduced in the aorta from WD rats (p < 0.01). These data show that fat feeding induces vascular oxidative stress and a reduction in endothelial function. Furthermore, there is a reduced capacity for both basal and stimulated vascular H2S production via CSE in fat fed rats.
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Vic, 3083, Australia.
authors.forename: Trisha A
authors.initials: TA
authors.lastname: Jenkins
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Vic, 3083, Australia.
authors.forename: Jason C D
authors.initials: JC
authors.lastname: Nguyen
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Vic, 3083, Australia. joanne.hart@rmit.edu.au.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Hart
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D059305:Diet, High-Fat; D066273:Diet, Western; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D015430:Weight Gain
chemical_list: D008562:Membrane Glycoproteins; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: Cystathionine-γ-lyase; Endothelial dysfunction; Hyperlipidaemia; NADPH oxidase