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Tetrahydrobiopterin does not affect end‐organ responsiveness to norepinephrine‐mediated vasoconstriction in aged skin
Author(s) -
Lang James A,
Bruning Rebecca S,
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.lb634
Subject(s) - medicine , endocrinology , adrenergic , microdialysis , vasoconstriction , norepinephrine , chemistry , vasodilation , perfusion , receptor , central nervous system , dopamine
We have recently found that tetrahydrobiopterin (BH 4 ), a cofactor in norepinephrine (NE) biosynthesis, offsets the attenuated reflex VC in aged skin. We hypothesize that localized BH 4 supplementation would not affect end‐organ VC responsiveness to exogenous NE after localized sympathetic nerve blockade. Two microdialysis fibers were placed in bretylium tosylate pretreated (presynaptically blocks neurotransmitters release from sympathetic adrenergic nerve terminals; iontophoresis, 200 μA for 20 min) forearm skin of 10 young (Y) and 10 older (O) subjects for perfusion of 1) Ringer's (control) and 2) 5 mM BH 4 . While local skin temperature was clamped at 34 o C, 6 randomized concentrations of NE (10 −12 , 10 −10 , 10 −8 , 10 −6 , 10 −4 , 10 −2 M) were infused at each drug‐treated site. Cutaneous vascular conductance was calculated (CVC = laser Doppler flux / MAP) and normalized to baseline (%ΔCVC base ). Despite prejunctional adrenergic blockade, NE‐mediated VC was blunted in aged skin at each NE dose (10 −12 : −12 ± 2 vs. −21 ± 2, 10 −10 : −15 ± 2 vs. −27 ± 1, 10 −8 : −22 ± 2 vs. −32 ± 2, 10 −6 : −27 ± 2 vs. −38 ± 1, 10 −4 : −52 ± 3 vs. −66 ± 5, 10 −2 : −62 ± 3 vs. −75 ± 4 %ΔCVC base ; P <0.01), and this response was not affected by pretreatment with BH 4 ( P >0.05). Localized BH 4 did not affect end‐organ responsiveness to exogenous NE suggesting that BH 4 augments VC primarily through the NE biosynthetic pathway in adrenergic nerve terminals.