Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms

Clinical Science - Tập 129 Số 2 - Trang 159-167 - 2015
Anna E. Stanhewicz1, Lacy M. Alexander1, W. Larry Kenney1
1Department of Kinesiology, Noll Laboratory, Pennsylvania State University, University Park, PA, U.S.A.

Tóm tắt

Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilatation. Folic acid and its metabolite, 5-methyltetrahydrofolate (5-MTHF), are reported to improve vessel function. We hypothesized that (i) local 5-MTHF administration and (ii) chronic folic acid supplementation would improve cutaneous microvascular function in ageing through NO-dependent mechanisms. There were two separate studies in which there were 11 young (Y: 22±1 years) and 11 older (O: 71±3 years) participants. In both studies, two intradermal microdialysis fibres were placed in the forearm skin for local delivery of lactated Ringer's solution with or without 5 mM 5-MTHF. Red cell flux was measured by laser-Doppler flowmetry. Cutaneous vascular conductance [CVC=red cell flux/mean arterial pressure] was normalized as percentage maximum CVC (%CVCmax) (28 mM sodium nitroprusside, local temperature 43°C). In study 1 after CVC plateaued during local heating, 20 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused at each site to quantify NO-dependent vasodilatation. The local heating plateau (%CVCmax: O=82±3 vs Y=96±1, P=0.002) and NO-dependent vasodilatation (%CVCmax: O=26±6% vs Y=49±5, P=0.03) were attenuated in older participants. 5-MTHF augmented the overall (%CVCmax=91±2, P=0.03) and NO-dependent (%CVCmax=43±9%, P=0.04) vasodilatation in older but not young participants. In study 2 the participants ingested folic acid (5 mg/day) or placebo for 6 weeks in a randomized, double-blind, crossover design. A rise in oral temperature of 1°C was induced using a water-perfused suit, body temperature was held and 20 mM L-NAME was perfused at each site. Older participants had attenuated reflex (%CVCmax: O=31±8 vs Y=44±5, P=0.001) and NO-dependent (%CVCmax: O=9±2 vs Y=21±2, P=0.003) vasodilatation. Folic acid increased CVC (%CVCmax=47±5%, P=0.001) and NO-dependent vasodilatation (20±3%, P=0.003) in the older but not the young participants. Both local perfusion of 5-MTHF and supplementation with folic acid increase vasodilatation in ageing individuals through NO-dependent mechanisms.

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Clinical Science

Tập 129 Số 2

159-167

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