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Localized tyrosine or tetrahydrobiopterin supplementation augments vasoconstriction in aged human skin
Author(s) -
Lang James A,
Holowatz Lacy A,
Kenney W Larry
Publication year - 2010
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.24.1_supplement.991.26
Subject(s) - tyramine , chemistry , tyrosine , vasoconstriction , tetrahydrobiopterin , microdialysis , endocrinology , medicine , biochemistry , cofactor , central nervous system , enzyme
Attenuated reflex vasoconstriction in aged skin may be partly mediated by oxidant‐induced reduction in functional substrate and cofactor availability for norepinephrine (NE) biosynthesis; tyrosine and tetrahydrobiopterin (BH 4 ), respectively. We hypothesize that localized supplementation of these in aged skin would augment reflex‐ (whole‐body cooling) and pharmacologically‐ (tyramine‐‐displaces NE from axon terminals) induced VC. Four microdialysis fibers were placed in the forearm skin of 10 young (Y: 20 yr) and 10 older (O: 72 yr) subjects for infusion of 1) Ringer's (control), 2) 0.5mM L‐tyrosine, 3) 5mM BH 4 , and 4) BH 4 + L‐tyrosine. Cutaneous vascular conductance was calculated (CVC = laser Doppler flux/MAP) and normalized to baseline (%ΔCVC base ). VC was attenuated at the control site in O during whole‐body cooling (Y: −39 ± 3, O: −17 ± 3 %ΔCVC base ; P <0.01) and tyramine perfusion (Y: −41 ± 3, O: −21 ± 4 %ΔCVC base ; P <0.01). Similar to BH 4 (cold, Y: −37 ± 3, O: −36 ± 3; tyramine, Y: 41 ± 2, O: −36 ± 3 %ΔCVC base ), tyrosine also augmented the VC in O during cooling (Y: −37 ± 4, O: −34 ± 4 %ΔCVC base ) and tyramine (Y: −40 ± 4, O: −45 ± 4 %ΔCVC base ), but BH 4 + tyrosine did not further augment VC during cooling (Y: −38 ± 4, O: −31 ± 3 %ΔCVC base ) or tyramine (Y: −36 ± 3, O: −36 ± 5 %ΔCVC base ). Localized tyrosine or BH 4 augmented VC in aged skin, suggesting that their reduced bioavailability may impair NE synthesis and contribute to attenuated VC.