LOCAL TETRAHYDROBIOPTERIN AUGMENTS REFLEX CUTANEOUS VASODILATION IN AGED HUMAN SKIN

Open Access
- Author:
- Stanhewicz, Anna E.
- Graduate Program:
- Physiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- July 06, 2011
- Committee Members:
- William Lawrence Kenney Jr., Thesis Advisor/Co-Advisor
William Lawrence Kenney Jr., Thesis Advisor/Co-Advisor
Lacy Marie Alexander, Thesis Advisor/Co-Advisor - Keywords:
- tetrahydrobiopterin
skin blood flow
aging - Abstract:
- Reflex cutaneous vasodilation (VD) is attenuated in aged skin, potentially resulting in decreased heat loss during heat exposure. Constitutive NO-synthase (NOS) is necessary for full expression of reflex cutaneous VD. Tetrahydrobiopterin (BH4) acts as an essential cofactor for NOS activity by preventing NOS uncoupling and reducing oxidant stress. Reduced BH4 bioavailability is associated with primary aging. We hypothesized that acute local BH4 administration would augment NO-dependent VD in aged skin during hyperthermia. Three intradermal microdialysis fibers were placed in the ventral forearm skin of 11 young (Y, 22 ±1 years) and 11 older (O, 73±2 years) human subjects for local infusion of (1) control: Ringers solution, (2) BH4 administration: 10mM BH4, and (3) NOS inhibition: 20mM NG-nitro-L-arginine methyl ester (L-NAME), 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 1ºC 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). VD was attenuated at the control site in O (O: 0.6 ± 0.1 vs. Y: 1.0 ± 0.2 CVC; p<0.05). BH4 administration increased VD in O (1.2 ± 0.2 CVC; p<0.05) but not Y (1.0 ± 0.2 CVC). NOS inhibition similarly attenuated VD at the BH4 site in both groups (O: 0.7 ± 0.1 vs. Y: 0.5 ± 0.1 CVC; p<0.05). BH4 administration increased absolute maximal CVC in O (BH4: 2.0 ± 0.2 vs. control: 1.4 ± 0.2 CVC; p<0.5). Acute local BH4 administration increases NO-dependant reflex cutaneous VD in aged skin during whole body heat stress, suggesting that reduced BH4 contributes to attenuated VD in older humans.