Localized tyrosine or tetrahydrobiopterin supplementation corrects the age-related decline in cutaneous vasoconstriction

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Abstract

The attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant-induced reduction in functional substrate and cofactor availability for noradrenaline biosynthesis. We hypothesized that localized supplementation of tyrosine and tetrahydrobiopterin (BH4) in aged human skin could augment reflex- (whole-body cooling) and pharmacologically (tyramine, which displaces noradrenaline from axon terminals) induced vasoconstriction. Four microdialysis fibres were placed in the forearm skin of 10 young and 10 older subjects for infusion of (1) Ringer solution (control), (2) 0.5 mm l-tyrosine, (3) 5 mm BH4, and (4) BH4+l-tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline (%ΔCVCbase). Vasoconstriction was attenuated at the control site in the older subjects during both whole-body cooling (young: -39 ± 3, older: -17 ± 3%ΔCVCbase; P < 0.01) and tyramine infusion (young: -41 ± 3, older: -21 ± 4%ΔCVCbase; P < 0.01). BH4 (cold, young: -37 ± 3, older: -36 ± 3; tyramine, young: -41 ± 2, older: -36 ± 3%ΔCVCbase) and tyrosine (cold, young: -37 ± 4, older: -34 ± 4; tyramine, young: -40 ± 4, older: -45 ± 4%ΔCVCbase) both resolved the age-related decrease in cutaneous vasoconstriction, but BH4+ tyrosine did not further augment vasoconstriction (cold, young: -38 ± 4, older: -31 ± 3; tyramine, young: -36 ± 3, older: -36 ± 5%ΔCVCbase). These data are consistent with the concept that reduced bioavailability of BH4 and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.

Original languageEnglish (US)
Pages (from-to)1361-1368
Number of pages8
JournalJournal of Physiology
Volume588
Issue number8
DOIs
StatePublished - Apr 1 2010

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Vasoconstriction
Tyrosine
Skin
Tyramine
Norepinephrine
Reflex
Microdialysis
Presynaptic Terminals
Vasoconstrictor Agents
Forearm
Oxidants
Biological Availability
Blood Vessels
sapropterin
Arterial Pressure
Lasers

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

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title = "Localized tyrosine or tetrahydrobiopterin supplementation corrects the age-related decline in cutaneous vasoconstriction",
abstract = "The attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant-induced reduction in functional substrate and cofactor availability for noradrenaline biosynthesis. We hypothesized that localized supplementation of tyrosine and tetrahydrobiopterin (BH4) in aged human skin could augment reflex- (whole-body cooling) and pharmacologically (tyramine, which displaces noradrenaline from axon terminals) induced vasoconstriction. Four microdialysis fibres were placed in the forearm skin of 10 young and 10 older subjects for infusion of (1) Ringer solution (control), (2) 0.5 mm l-tyrosine, (3) 5 mm BH4, and (4) BH4+l-tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline ({\%}ΔCVCbase). Vasoconstriction was attenuated at the control site in the older subjects during both whole-body cooling (young: -39 ± 3, older: -17 ± 3{\%}ΔCVCbase; P < 0.01) and tyramine infusion (young: -41 ± 3, older: -21 ± 4{\%}ΔCVCbase; P < 0.01). BH4 (cold, young: -37 ± 3, older: -36 ± 3; tyramine, young: -41 ± 2, older: -36 ± 3{\%}ΔCVCbase) and tyrosine (cold, young: -37 ± 4, older: -34 ± 4; tyramine, young: -40 ± 4, older: -45 ± 4{\%}ΔCVCbase) both resolved the age-related decrease in cutaneous vasoconstriction, but BH4+ tyrosine did not further augment vasoconstriction (cold, young: -38 ± 4, older: -31 ± 3; tyramine, young: -36 ± 3, older: -36 ± 5{\%}ΔCVCbase). These data are consistent with the concept that reduced bioavailability of BH4 and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.",
author = "Lang, {James A.} and Alexander, {Lacy Marie} and {Kenney, Jr.}, {William Lawrence}",
year = "2010",
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T1 - Localized tyrosine or tetrahydrobiopterin supplementation corrects the age-related decline in cutaneous vasoconstriction

AU - Lang, James A.

AU - Alexander, Lacy Marie

AU - Kenney, Jr., William Lawrence

PY - 2010/4/1

Y1 - 2010/4/1

N2 - The attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant-induced reduction in functional substrate and cofactor availability for noradrenaline biosynthesis. We hypothesized that localized supplementation of tyrosine and tetrahydrobiopterin (BH4) in aged human skin could augment reflex- (whole-body cooling) and pharmacologically (tyramine, which displaces noradrenaline from axon terminals) induced vasoconstriction. Four microdialysis fibres were placed in the forearm skin of 10 young and 10 older subjects for infusion of (1) Ringer solution (control), (2) 0.5 mm l-tyrosine, (3) 5 mm BH4, and (4) BH4+l-tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline (%ΔCVCbase). Vasoconstriction was attenuated at the control site in the older subjects during both whole-body cooling (young: -39 ± 3, older: -17 ± 3%ΔCVCbase; P < 0.01) and tyramine infusion (young: -41 ± 3, older: -21 ± 4%ΔCVCbase; P < 0.01). BH4 (cold, young: -37 ± 3, older: -36 ± 3; tyramine, young: -41 ± 2, older: -36 ± 3%ΔCVCbase) and tyrosine (cold, young: -37 ± 4, older: -34 ± 4; tyramine, young: -40 ± 4, older: -45 ± 4%ΔCVCbase) both resolved the age-related decrease in cutaneous vasoconstriction, but BH4+ tyrosine did not further augment vasoconstriction (cold, young: -38 ± 4, older: -31 ± 3; tyramine, young: -36 ± 3, older: -36 ± 5%ΔCVCbase). These data are consistent with the concept that reduced bioavailability of BH4 and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.

AB - The attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant-induced reduction in functional substrate and cofactor availability for noradrenaline biosynthesis. We hypothesized that localized supplementation of tyrosine and tetrahydrobiopterin (BH4) in aged human skin could augment reflex- (whole-body cooling) and pharmacologically (tyramine, which displaces noradrenaline from axon terminals) induced vasoconstriction. Four microdialysis fibres were placed in the forearm skin of 10 young and 10 older subjects for infusion of (1) Ringer solution (control), (2) 0.5 mm l-tyrosine, (3) 5 mm BH4, and (4) BH4+l-tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline (%ΔCVCbase). Vasoconstriction was attenuated at the control site in the older subjects during both whole-body cooling (young: -39 ± 3, older: -17 ± 3%ΔCVCbase; P < 0.01) and tyramine infusion (young: -41 ± 3, older: -21 ± 4%ΔCVCbase; P < 0.01). BH4 (cold, young: -37 ± 3, older: -36 ± 3; tyramine, young: -41 ± 2, older: -36 ± 3%ΔCVCbase) and tyrosine (cold, young: -37 ± 4, older: -34 ± 4; tyramine, young: -40 ± 4, older: -45 ± 4%ΔCVCbase) both resolved the age-related decrease in cutaneous vasoconstriction, but BH4+ tyrosine did not further augment vasoconstriction (cold, young: -38 ± 4, older: -31 ± 3; tyramine, young: -36 ± 3, older: -36 ± 5%ΔCVCbase). These data are consistent with the concept that reduced bioavailability of BH4 and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.

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