January 1, 2009Open Access
View Full PaperB6D2F1 Mice Are a Suitable Model of Oxidative Stress-Mediated Impaired Endothelium-Dependent Dilation With Aging
Structured PICO
Are B6D2F1 mice a suitable model for investigating oxidative stress-mediated impaired endothelium-dependent dilation with aging?
P
Population
B6D2F1 mice at 6.9 +/- 0.3 and 31.9 +/- 0.6 months of age
I
Intervention
Aging (31.9 +/- 0.6 months) and pharmacological assessment with acetylcholine, TEMPOL, and l-NAME
C
Comparator
Young mice (6.9 +/- 0.3 months)
O
Outcome
Endothelium-dependent dilation (EDD) to acetylcholine (ACh) in isolated carotid and femoral arteriessurrogate
B6D2F1 mice demonstrate age-related, oxidative stress-mediated impairment in endothelium-dependent dilation and increased arterial stiffness, making them a suitable model for vascular 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.