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Local 5‐methyltetrahydrofolate administration augments NO‐dependent vasodilation in aged human skin (1106.11)
Author(s) -
Stanhewicz Anna,
Alexander Lacy,
Kenney W.
Publication year - 2014
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.28.1_supplement.1106.11
Subject(s) - vasodilation , microdialysis , medicine , nitric oxide , metabolite , forearm , pharmacology , endocrinology , surgery , central nervous system
Even in the absence of overt cardiovascular disease, older men and women have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)‐dependent cutaneous vasodilation (VD) during local heating. Folic acid and its metabolite 5‐methyltetrahydrofolate (5‐MTHF) improve conduit vessel function, possibly through NO‐dependent mechanisms. We hypothesized that local 5‐MTHF administration would augment NO‐dependent VD in aged skin. Two intradermal microdialysis fibers were placed in the forearm skin of 7 young (Y, 23±1 years) and 7 older (O, 77±3 years) subjects for local delivery of Ringer’s solution (control) or 5mM 5‐MTHF. Red cell flux was measured over each site by laser‐Doppler flowmetry (LDF) during standardized local heating to 42°C. After cutaneous vascular conductance (CVC = LDF/MAP) plateaued, 20mM L‐NAME was perfused at each site to quantify NO‐dependent VD. Data were normalized as %CVCmax (28mM SNP and local heat, 43°C). Local heating plateau (O: 82±3 vs. Y: 96±1%CVCmax; p=0.002) and NO‐dependent VD (O: 26±6 vs. Y: 49±5%CVCmax; p=0.03) were attenuated at the control site in O. 5‐MTHF administration augmented overall (91±2%CVCmax; p=0.03) and NO‐dependent (43±9%CVCmax; p=0.04) VD in O but not Y. Local 5‐MTHF administration restores cutaneous VD through augmented NO‐dependent VD, suggesting that exogenous 5‐MTHF increases NO synthesis in aged cutaneous microvasculature. Grant Funding Source : Supported by NIH RO1‐AG07004‐25