B6D2F1 mice are a suitable model of oxidative stress-mediated impaired endothelium-dependent dilation with aging

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. N G -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. © The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.