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Localized tyrosine or tetrahydrobiopterin supplementation corrects the age‐related decline in cutaneous vasoconstriction
Author(s) -
Lang James A.,
Holowatz Lacy A.,
Kenney W. Larry
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.185694
Subject(s) - vasoconstriction , tyramine , tyrosine , medicine , endocrinology , vasodilation , chemistry , biochemistry
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 (BH 4 ) 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 m m l ‐tyrosine, (3) 5 m m BH 4 , and (4) BH 4 + l ‐tyrosine. Cutaneous vascular conductance (CVC) was calculated (laser Doppler flux/mean arterial pressure) and normalized to baseline (%ΔCVC base ). Vasoconstriction was attenuated at the control site in the older subjects during both whole‐body cooling (young: −39 ± 3, older: −17 ± 3%ΔCVC base ; P < 0.01) and tyramine infusion (young: −41 ± 3, older: −21 ± 4%ΔCVC base ; P < 0.01). BH 4 (cold, young: −37 ± 3, older: −36 ± 3; tyramine, young: −41 ± 2, older: −36 ± 3%ΔCVC base ) and tyrosine (cold, young: −37 ± 4, older: −34 ± 4; tyramine, young: −40 ± 4, older: −45 ± 4%ΔCVC base ) both resolved the age‐related decrease in cutaneous vasoconstriction, but BH 4 + tyrosine did not further augment vasoconstriction (cold, young: −38 ± 4, older: −31 ± 3; tyramine, young: −36 ± 3, older: −36 ± 5%ΔCVC base ). These data are consistent with the concept that reduced bioavailability of BH 4 and/or tyrosine may impair noradrenaline synthesis and contribute to the attenuated vasoconstrictor response in aged skin.