title: Sodium nitrite de-stiffening of large elastic arteries with aging: role of normalization of advanced glycation end-products.
abstract: 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 (26-28months) compared with young (4-6months) control animals (520±9 vs. 405±6cm/s, p<0.05), and this was reversed by 3weeks of sodium nitrite treatment (50mg/L) (435±17cm/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 β 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 (10μM), 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.
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. bradley.fleenor@colorado.edu
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Fleenor
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Jason S
authors.initials: JS
authors.lastname: Eng
authors.forename: Devatha P
authors.initials: DP
authors.lastname: Nair
authors.forename: R Blair
authors.initials: RB
authors.lastname: Dodson
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004548:Elasticity / Q000187:drug effects / Q000502:physiology; D004549:Elastin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011748:Pyrogallol / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D016212:Transforming Growth Factor beta; D011748:Pyrogallol; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D004549:Elastin; D012977:Sodium Nitrite