Sodium nitrite de-stiffening of large elastic arteries with aging: role of normalization of advanced glycation end-products

Exp Gerontol. 2012 Aug;47(8):588-94. doi: 10.1016/j.exger.2012.05.004. Epub 2012 May 12.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidants / pharmacology
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / physiology
  • Collagen Type I / metabolism
  • Drug Evaluation, Preclinical / methods
  • Elasticity / drug effects
  • Elasticity / physiology
  • Elastin / metabolism
  • Glycation End Products, Advanced / metabolism*
  • Glycation End Products, Advanced / pharmacology
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Pyrogallol / pharmacology
  • Sodium Nitrite / pharmacology*
  • Superoxides / metabolism
  • Tissue Culture Techniques
  • Transforming Growth Factor beta / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Vascular Stiffness / drug effects*
  • Vascular Stiffness / physiology

Substances

  • Antioxidants
  • Collagen Type I
  • Glycation End Products, Advanced
  • Transforming Growth Factor beta
  • Pyrogallol
  • Superoxides
  • 3-nitrotyrosine
  • Tyrosine
  • Elastin
  • Sodium Nitrite