期刊
EXPERIMENTAL GERONTOLOGY
卷 47, 期 8, 页码 588-594出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2012.05.004
关键词
Arterial stiffness; Collagen; Elastin; Nitrotyrosine; Superoxide
资金
- [AG013038]
- [AG000279]
- [HL007822]
We tested the hypothesis that sodium nitrite treatment reverses large elastic artery stiffening in old mice via reductions in collagen I, increases in elastin and/or decreases in advanced glycation end products (AGEs) mediated by reduced oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large elastic artery stiffness, was greater in old (26-28 months) compared with young (4-6 months) control animals (520 +/- 9 vs. 405 +/- 6 cm/s, p<0.05), and this was reversed by 3 weeks of sodium nitrite treatment (50 mg/L) (435 +/- 17 cm/s). Age-related increases (p<0.05) in aortic superoxide production were associated with greater total and adventitial nitrotyrosine staining, all of which were reversed by nitrite treatment. Total and adventitial transforming growth factor beta and collagen I were increased, and total and medial elastin were reduced with aging (p<0.05), but were unaffected by sodium nitrite. Aorta from old mice had increased total, adventitial and medial AGEs (p<0.05 vs. young), which were normalized by sodium nitrite treatment. In aortic segments from young mice in vitro, pyrogallol (10 mu M), a superoxide generator, induced an aging-like increase in AGEs, and direct treatment with AGEs induced vascular stiffening; these effects were prevented by incubation with sodium nitrite. De-stiffening of aged large elastic arteries by short-term sodium nitrite therapy is mediated in part by normalization of AGEs secondary to amelioration of oxidative stress. (C) 2012 Elsevier Inc. All rights reserved.
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