Local tetrahydrobiopterin supplementation augments reflex cutaneous vasodilaton in aged human skin

NO‐synthase (NOS) is necessary for full expression of reflex cutaneous vasodilation (VD). Tetrahydrobiopterin (BH 4 ) is an essential cofactor for NOS. Reduced BH 4 bioavailability is associated with aging. We hypothesized that acute local BH 4 supplementation would augment NO‐dependent VD in aged skin during hyperthermia. Three intradermal microdialysis fibers were placed in the forearm skin of 10 young (Y, 24 ± 6 years) and 7 older (O, 72 ± 6 years) human subjects for local infusion of Ringers solution (control), L‐NAME (NOS‐inhibition) and 10mM BH 4 , respectively. Red cell flux was measured at each site by laser‐Doppler flowmetry (LDF) as reflex VD was induced using a water perfused suit. After a 1°C rise in oral temperature, mean body temperature was clamped and L‐NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and expressed as percent of maximum (%CVCmax: infusion of 28mM sodium nitroprusside). VD was attenuated at control site in O (O: 35 ± 6 vs. Y: 54 ± 7 %CVCmax; p<0.05). BH 4 supplementation augmented VD in O (54 ± 11 %CVCmax; p<0.05) but not Y (57 ± 8 %CVCmax; p<0.05). NOS inhibition equally attenuated VD at the BH 4 site in both groups (O: 38 ± 4 vs. Y: 24 ± 5 %CVCmax; p<0.05). Acute local BH 4 supplementation augments reflex NO‐dependant VD in aged skin, suggesting that reduced BH 4 bioavailability contributes to the attenuated VD in older humans. Supported by: NIH AG007‐004‐20