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Am J Physiol Heart Circ Physiol (August 11, 2006). doi:10.1152/ajpheart.00648.2006
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Submitted on June 16, 2006
Accepted on August 4, 2006

Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin

Lacy A. Holowatz1*, Caitlin S. Thompson1, and W. Larry Kenney2

1 Kinesiology, Penn State, University Park, Pennsylvania, United States
2 Physiology and Kinesiology, Pennsylvania State University, University Park, United States

* To whom correspondence should be addressed. E-mail: lma191{at}psu.edu.

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated in older humans. NO bioavailability in aged skin may be decreased by an age-related increase in reactive oxygen species (ROS) or a decrease in L-arginine availability via upregulated arginase, leading to NO-synthase uncoupling and further ROS production. The purpose of this study was to determine the effect of acute ascorbate administration alone and combined with arginase inhibition on attenuated reflex VD in aged skin. Eleven young (Y, 22±1 years) and 10 older (O, 68±1 years) subjects were instrumented with four intradermal microdialysis (MD) fibers. MD sites served as control (Co), NO-synthase inhibited (NOS-I: 10mM L-NAME), L-ascorbate supplemented (Asc: 10mM L-ascorbate), and Asc+arginase-inhibited (AA+A-I: 10mM L-ascorbate+5mM BEC+5mM nor-NOHA). After baseline measurements, subjects underwent whole-body heating with a water-perfused suit to increase oral temperature (Tor) by 0.8-1.0°C. Red blood cell flux was measured using laser-Doppler flowmetry over each MD site, and cutaneous vascular conductance was calculated (CVC=flux/mean arterial pressure) and normalized to maximal CVC (28mM sodium nitroprusside + local heating to 43°C). Cutaneous VD during heating was attenuated in O (Y: 37±3 vs. O: 28±3%CVCmax, p<0.05). NOS-I decreased VD in both groups compared to Co (Y: 20±4, O: 15±2%CVCmax, p<0.05 vs. Co within group). Asc and Asc+A-I increased VD beyond control in O (Asc: 35±4%CVCmax, Asc+A-I: 41±3%CVCmax; p<0.001) but did not in Y (Asc: 36±3%CVCmax ; Asc+A-I: 40±5%CVCmax, p>0.05 ). Combined Asc+A-I resulted in a greater increase in VD than did Asc alone in O (p=0.001). Acute Asc increased reflex cutaneous VD in aged skin. When combined with arginase inhibition to increase L-arginine availability Asc supplentation resulted in a further increase in VD above Asc alone, effectively augmenting CVC to the level of young subjects.




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