Nitrite supplementation reverses vascular endothelial dysfunction in old mice via improved nitric oxide bioavailability

Aging causes vascular endothelial dysfunction as indicated by impaired endothelium‐dependent dilation (EDD), and this is mediated by reduced nitric oxide (NO) bioavailability. Administration of nitrite (NO 2 − ), a product of NO oxidation, is associated with enhanced NO bioavailability. We hypothesized that treatment with NO 2 − would enhance EDD with aging. Old (27 mo, n = 7) adult C57 male mice had a lower ex vivo carotid artery acetylcholine (ACh)‐induced EDD (70.9 ± 3.7 vs. 94.0 ± 2.9%, P < 0.05) and NO component of EDD (mean dilation to ACh + L‐name minus mean dilation to ACh alone, −26.6 ± 5.9 vs. −50.5 ± 9.5%, P < 0.05) compared with young adult controls (6 mo, n = 6). In old mice (n = 4), 3 weeks of dietary supplementation with sodium NO 2 − (50 mg/l in drinking water) restored EDD (96.6 ± 1.9%, P < 0.05) and its NO component (−60.2 ± 5.0%, P < 0.001). Sensitivity to ACh and endothelium‐independent dilation were not different in young, old and old NO 2 − supplemented mice. These preliminary results support the idea that NO 2 − supplementation may be an effective strategy for reversing vascular endothelial dysfunction with aging by enhancing NO bioavailability. Work supported by NIH R37 AG013038, HL 007822