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Pyridoxamine attenuates age‐related impairments in cerebral artery endothelial function
Author(s) -
Walker Ashley E.,
Meza Antonio E.,
Earl Alex E.,
Machin Daniel R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.711.12
Subject(s) - pyridoxamine , medicine , endothelial dysfunction , endothelium , oxidative stress , endocrinology , vitamin , vitamin b6
Age‐related impairments to cerebral artery endothelial function are thought to be a key contributor to the increased risk for cerebrovascular diseases that occur with advancing age. However, there are a limited number of clinical interventions to prevent age‐related cerebral artery endothelial dysfunction. A novel potential intervention is to prevent advanced glycation end‐product (AGE) formation with pyridoxamine. AGEs can increase oxidative stress and reduce nitric oxide (NO) bioavailability, potentially leading to endothelial dysfunction. Pyridoxamine, a natural form of vitamin B6, prevents the conversion of stable sugar‐protein adducts (Amadori compounds) to AGEs. Thus, we sought to determine if long‐term pyridoxamine treatment initiated in middle‐age can prevent age‐related cerebral artery endothelial dysfunction and preserve NO bioavailability. We administered pyridoxamine (2 g/L in drinking water) or vehicle control for 6 months to C57BL/6 mice. We assessed cerebral artery endothelial function by endothelium‐dependent dilation (EDD, maximal response to acetylcholine) in the middle cerebral artery (MCA) of old pyridoxamine‐treated (n=11, 24.8±0.2 mo), old vehicle control‐treated (n=10, 24.8±0.2 mo), and young untreated (n=7, 7.4±0.0 mo) mice. MCA EDD was lower in old vehicle control compared to young untreated mice (30.5±3.9% vs. 50.0±4.8%, p=0.003). However, MCA EDD of old pyridoxamine‐treated mice was partially preserved compared with old vehicle control mice (42.5±4.5%, p=0.03), but was not different from the young untreated mice (p=0.29). After incubation with NO synthase inhibitor L‐NAME, the dilatory response was not differ between groups (p>0.05), indicating that increased NO bioavailability mediated the preservation of MCA EDD by pyridoxamine in old mice. Endothelium‐independent dilation was not different between groups (p>0.05). In conclusion, long‐term pyridoxamine treatment preserves, at least in part, cerebral artery endothelial function and NO bioavailability with advancing age. Support or Funding Information NIH AG046326 and a University of Utah Center on Aging Pilot Award This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .