Advanced Glycation End‐Products in Age‐Related Arterial Stiffening: Modulation by Sodium Nitrite

Abstract

Aging causes large elastic artery stiffening and this is associated with oxidative stress and increased advanced glycation end‐products (AGEs). We tested the hypothesis that vascular oxidative stress with aging induces AGEs, which increase intrinsic mechanical stiffness, and that sodium nitrite prevents this stiffening. Old (O, 27 mo, n=4) vs. young (Y, 6 mo, n=4) control male C57Bl/6N mice had greater (p<0.05) nitrotyrosine abundance (5.0 ± 1.1 vs. 1.0 ± 0.3 AU), a marker of oxidative stress, and AGEs (2.1 ± 0.2 vs.1.0 ± 0.1 AU) (p<0.05). Sodium nitrite treatment (50 mg/L in drinking water, 3 weeks) in O reduced (p<0.05) aortic nitrotyrosine (1.9 ± 0.6 AU) and AGEs (1.2 ± 0.2 AU). Stimulation of superoxide‐induced oxidative stress ex vivo with pyrogallol (10μM, 72 hr) in aortic segments from Y mice increased AGEs (2.3 ± 0.5 vs. 1.0 ± 0.1 AU, p<0.05), an effect prevented by treatment with sodium nitrite (1.1 ± 0.2 AU). Aortic rings from Y mice treated with AGEs (100μg/mL, 72 hrs) had a greater elastic modulus, a measure of mechanical stiffness, compared with control (3984 ± 236 vs. 2074 ± 218 KPa, p<0.05), and sodium nitrite prevented this effect (2148 ± 446 KPa). These results suggest that AGEs, induced by excessive superoxide‐associated oxidative stress, contributes to aortic stiffening with aging in mice. AGEs‐induced aortic stiffness may be preventable with sodium nitrite supplementation.