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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 10, 2009

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/gln049
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

B6D2F1 Mice Are a Suitable Model of Oxidative Stress–Mediated Impaired Endothelium-Dependent Dilation With Aging

Lisa A. Lesniewski, Melanie L. Connell, Jessica R. Durrant, Brian J. Folian, Martin C. Anderson, Anthony J. Donato and Douglas R. Seals

Department of Integrative Physiology, University of Colorado at Boulder

Address correspondence to Lisa Lesniewski, PhD, Department of Integrative Physiology, University of Colorado at Boulder, 354 UCB, Boulder, CO 80309. Email: Lisa.Lesniewski{at}colorado.edu


   Abstract

To determine if B6D2F1 mice represent a suitable model of oxidative stress–mediated impaired endothelium-dependent dilation (EDD) with aging, mice were studied at 6.9 ± 0.3 and 31.9 ± 0.6 months. EDD to acetylcholine (ACh) was 26% (p < .001) and 12% (p < .001) lower, respectively, in isolated carotid (n = 10–11) and femoral (n = 10) arteries from older mice, and reductions in arterial pressure to systemic ACh infusion were smaller in older mice (n = 6–10; p < .01). Nitrotyrosine was marked in aorta of older mice (p < .05, n = 4). Superoxide production in carotid arteries was greater (p < .05), and TEMPOL restored dilation in carotid arteries and systemically in older mice. NG-nitro-L-arginine methyl ester (L-NAME) reduced carotid artery dilation in young more than older mice, whereas TEMPOL restored the effects of L-NAME in older mice. Carotid artery stiffness was increased in older compared with young mice (p = .04). Our results provide the first comprehensive evidence that B6D2F1 mice are a useful model for investigating mechanisms of reduced nitric oxide–dependent, oxidative stress–associated EDD and increased arterial stiffness with aging.

Keywords Superoxide; Arterial stiffness; Carotid artery; Femoral artery; Nitrotyrosine

Received: June 10, 2008; Accepted: August 27, 2008


Decision Editor: Huber R. Warner, PhD


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