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The Journal of Physiology
Article . 2009 . Peer-reviewed
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Local tetrahydrobiopterin administration augments cutaneous vasoconstriction in aged humans

Authors: James A, Lang; Lacy A, Holowatz; W Larry, Kenney;

Local tetrahydrobiopterin administration augments cutaneous vasoconstriction in aged humans

Abstract

Reflex vasoconstriction (VC) is attenuated in aged skin resulting in greater skin blood flow and heat loss during cold exposure. We hypothesized that adrenergic function is compromised due to depletion of tetrahydrobiopterin (BH4), an essential cofactor required for catecholamine synthesis, and therefore local BH4 supplementation would functionally augment reflex and pharmacologically induced VC elicited by gradual whole‐body cooling (skin temperature (Tsk) = 30.5°C) and tyramine infusion, respectively. Four microdialysis (MD) fibres were placed in the forearm skin of 11 young (Y) and 11 older (O) human subjects for infusion of (1) Ringer solution (control), (2) 5 mm BH4, (3) 5 mm BH4+ 10 mm ascorbate, and (4) 5 mm BH4+ adrenoreceptor blockade (5 mm yohimbine + 1 mm propranolol). Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance was calculated as CVC = LDF/MAP and expressed as per cent change from baseline (%ΔCVCbase). The VC response was lower at the control site in O during cooling (Y: −34 ± 2%ΔCVCbase, O: −17 ± 2%ΔCVCbase; P < 0.001) and tyramine infusion (Y: −33 ± 4%ΔCVCbase, O: −15 ± 3%ΔCVCbase; P < 0.001). BH4 infusion normalized O to Y values during both cooling (Y: −34 ± 4%ΔCVCbase, O: −34 ± 2%ΔCVCbase; P < 0.001) and tyramine (Y: −38 ± 4%ΔCVCbase, O: −35 ± 3%ΔCVCbase; P < 0.001), however, adding adrenoreceptor blockade abolished VC in aged skin indicating that BH4 acts through adrenergic, not cotransmitter, mechanisms. Local BH4 supplementation augments reflex and tyramine‐induced VC in aged skin, suggesting that reduced BH4 bioavailability may contribute to attenuated VC during whole‐body cooling.

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Keywords

Adult, Male, Aging, Adrenergic beta-Antagonists, Tyramine, Yohimbine, Propranolol, Body Temperature, Cold Temperature, Biopterins, Regional Blood Flow, Vasoconstriction, Humans, Female, Nitric Oxide Synthase, Sympathomimetics, Adrenergic alpha-Antagonists, Aged, Skin

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    28
    popularity
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    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
28
Average
Top 10%
Top 10%
bronze