Western-type diet induces senescence, modifies vascular function in non-senescence mice and triggers adaptive mechanisms in senescent ones.
The effects of high-fat diet ingestion on senescence-induced modulation of contractile responses to phenylephrine (Phe) were determined in aortas of senescence-accelerated (SAMP8) and non-senescent (SAMR1) mice fed (8weeks) a Western-type high-fat diet (WD). Increased levels of senescence-associated β-galactosidase staining were found in aortas of SAMP8 and SAMR1 with WD. In SAMR1, WD did not modify Phe contraction in spite of inducing major changes in the mechanisms of regulation of contractile responses. Although WD increased NAD(P)H-oxidase-derived O2(-) and augmented peroxynitrite formation, we found an increase of inducible NOS (iNOS)-derived NO production which may contribute to maintain Phe contraction in SAMR1 WD. On SAMP8, WD significantly decreased Phe-induced contractions when compared with SAMP8 under normal chow. This response was not dependent on changes of NOS expression, but rather as consequence of increased antioxidant capacity by superoxide dismutase (SOD1). A similar constrictor influence from cyclooxygenase (COX) pathway on Phe responses was found in SAMR1 and SAMP8 ND. However, WD removed that influence on SAMR1, and produced a switch in the balance from a vasoconstrictor to a vasodilator component in SAMP8. These results were associated to the increased COX-2 expression, suggesting that a COX-2-derived vasodilator prostaglandin may contribute to the vascular adaptations after WD intake. Taken together, our data suggest that WD plays a detrimental role in the vasculature of non-senescent mice by increasing pro-inflammatory (iNOS) and pro-oxidative signaling pathways and may contribute to increase vascular senescence. In senescent vessels, however, WD triggers different intrinsic compensatory alterations which include increase of antioxidant activity by SOD1 and vasodilator prostaglandin production via COX-2.
Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.
Yara
Y
Onetti
Francesc
F
Jiménez-Altayó
Magda
M
Heras
Elisabet
E
Vila
Ana Paula
AP
Dantas
D000222:Adaptation, Physiological; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D016922:Cellular Senescence / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006861:Hydrogen Peroxide / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases
Endothelium; High-fat diet; Nitric oxide; Prostaglandins; Vascular senescence