title: Aging compounds western diet-associated large artery endothelial dysfunction in mice: prevention by voluntary aerobic exercise.
abstract: We tested the hypothesis that aging will exacerbate the negative vascular consequences of exposure to a common physiological stressor, i.e., consumption of a "western" (high fat/high sucrose) diet (WD), by inducing superoxide-associated reductions in nitric oxide (NO) bioavailability, and that this would be prevented by voluntary aerobic exercise. Incremental stiffness and endothelium-dependent dilation (EDD) were measured in the carotid arteries of young (5.4±0.3 mo, N=20) and old (30.4±0.2 mo, N=19) male B6D2F1 mice fed normal chow (NC: 17% fat, 0% sucrose) or a western diet (40% fat, 19% sucrose) and housed in either standard cages or cages equipped with running wheels for 10-14 weeks. Incremental stiffness was higher in old NC (P<0.05) and both young (P<0.01) and old (P<0.01) WD fed mice compared with young NC mice, but WD did not further increase stiffness in the old mice. In cage control mice, maximal EDD was 17% lower in both NC fed old mice and young WD fed mice (P<0.05). Consumption of WD by old mice led to a further 20% reduction in maximal EDD (P<0.05). Incremental stiffness was 28% lower and maximal EDD was 38% greater in old WD fed mice with access to running wheels vs. old WD fed control mice (P<0.05) and not different from young NC fed controls. Wheel running also tended to improve maximal EDD (+9%, P=0.11), but not incremental stiffness in young WD fed mice. Ex vivo treatment with the superoxide scavenger TEMPOL and NO inhibitor l-NAME abolished these respective effects of age, WD and voluntary running on EDD. Ingestion of a WD induces similar degrees of endothelial dysfunction in old and young adult B6D2F1 mice, and these effects are mediated by a superoxide-dependent impairment of NO bioavailability. However, the combination of old age and WD, a common occurrence in our aging society, results in a marked, additive reduction in endothelial function. Importantly, regular voluntary aerobic exercise reduces arterial stiffness and protects against the adverse influence of WD on endothelial function in old animals by preventing superoxide suppression of NO. These findings may have important implications for arterial aging and the prevention of age-associated cardiovascular diseases.
authors: Department of Integrative Physiology, University of Colorado Boulder, 354 UCB, Boulder, CO 80309, United States; School of Medicine, Department of Internal Medicine, Division of Geriatrics, University of Utah, United States; Geriatrics Research Education and Clinical Center, Veterans Administration Medical Center, Salt Lake City Health Care System, 500 Foothill Dr., Salt Lake City, UT 84148, United States. Electronic address: Lisa.Lesniewski@utah.edu.
authors: Lisa A
authors: LA
authors: Lesniewski
authors: Melanie L
authors: ML
authors: Zigler
authors: Jessica R
authors: JR
authors: Durrant
authors: Molly J
authors: MJ
authors: Nowlan
authors: Brian J
authors: BJ
authors: Folian
authors: Anthony J
authors: AJ
authors: Donato
authors: Douglas R
authors: DR
authors: Seals
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D059289:Vascular Stiffness / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester
keywords: Aging; Exercise; Obesity; Vasodilation; Western diet
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