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Am J Physiol Heart Circ Physiol 291: H2965-H2970, 2006. First published August 11, 2006; doi:10.1152/ajpheart.00648.2006
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Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin

Lacy A. Holowatz,1 Caitlin S. Thompson,1 and W. Larry Kenney1,2

1Noll Laboratory, Department of Kinesiology; and 2Graduate Program in Physiology, Pennsylvania State University, University Park, Pennsylvania

Submitted 16 June 2006 ; accepted in final form 4 August 2006

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated in older humans. NO may be decreased by an age-related increase in reactive oxygen species or a decrease in L-arginine availability via upregulated arginase. The purpose of this study was to determine the effect of acute antioxidant supplementation alone and combined with arginase inhibition on reflex VD in aged skin. Eleven young (Y; 22 ± 1 yr) and 10 older (O; 68 ± 1 yr) human subjects were instrumented with four intradermal microdialysis (MD) fibers. MD sites were control (Co), NO synthase inhibited (NOS-I), L-ascorbate supplemented (Asc), and Asc + arginase-inhibited (Asc + A-I). After baseline measurements, subjects underwent whole body heating to increase oral temperature (Tor) by 0.8°C. Red blood cell flux was measured by using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal (CVCmax). 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 with Co (Y: 20 ± 4; O: 15 ± 2% CVCmax; P < 0.05 vs. Co within group). Asc and Asc + A-I increased VD beyond Co in O (Asc: 35 ± 4% CVCmax; Asc + A-I: 41 ± 3% CVCmax; P < 0.001) but 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 Asc alone in O (P = 0.001). Acute Asc supplementation increased reflex VD in aged skin. Asc combined with arginase inhibition resulted in a further increase in VD above Asc alone, effectively restoring CVC to the level of young subjects.

skin blood flow; aging; temperature regulation; antioxidant; vitamin C



Address for reprint requests and other correspondence: L. A. Holowatz, 123 Noll Laboratory, Pennsylvania State Univ., University Park, PA 16802 (e-mail: lma191{at}psu.edu)




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