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First published online on May 4, 2006.
 Copyright © 2006 by The Physiological Society
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Received March 6, 2006
Revised April 5, 2006
Accepted after revision April 28, 2006

L-arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin

Lacy A. Holowatz1*, Caitlin S Thompson1, and W. Larry Kenney1

1 The Pennsylvania State University

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

Full expression of reflex cutaneous vasodilatation is dependent on nitric oxide (NO) and vasodilatation is attenuated in healthy older humans. NO bioavailability in aged skin may be decreased by an age-related upregulation of arginase (Arg), which reciprocally regulates the NO-synthase (NOS) substrate L-arginine (L-arg). We hypothesized that increased Arg activity contributes to attenuated vasodilatation in aged skin by limiting L-arg for NOS-mediated NO synthesis. Five microdialysis fibres were placed in forearm skin of 10 young (Y: 23±1 years) and 9 older (O: 68±1 years) human subjects serving as control (C: Ringers), NOS-inhibited (10.0mM NG-nitro-L-arginine), Arg-inhibited (5.0mM (S)-(2-boronoethyl)-L-cysteine + 5.0mM N-hydroxy-nor-L-arginine), L-arg supplemented (L-arg: 10.0mM L-arginine) and combined Arg-inhibited + L-arg sites. After 20 min thermoneutral baseline, cutaneous vasodilatation was induced by passive whole body heating to increase oral temperature (Tor) by 1.0°C. Red blood cell flux was measured by laser-Doppler flowmetry over each microdialysis site. Cutaneous vascular conductance was calculated (CVC=flux/mean arterial pressure) and normalized to maximal CVC (CVCmax: 28.0mM sodium nitroprusside + local heating to 43°C). Cutaneous vasodilatation during heating was attenuated in O (Y: 42±1 vs. O: 30±1%CVCmax, p<0.001) at control sites. NOS inhibition decreased vasodilatation in both age groups compared to C (Y: 22±2, O: 18±2%CVCmax, p<0.001). Arg inhibition, L-arg supplementation, and Arg inhibition + L-arg supplementation augmented vasodilatation in O (Arg-inhibited: 46±4, L-arg: 44±4, Arg-inhibited + L-arg: 46±5%CVCmax, p<0.001 vs. C) but not in Y (Arg-inhibited: 46±4, L-arg: 38±4, Arg-inhibited + L-arg: 44±4%CVCmax, p>0.05 vs. C). Increasing L-arg for NO synthesis by either Arg inhibition or direct L-arg supplementation restores the age-related deficit in reflex cutaneous vasodilatation.


Key words: Ageing • Nitric oxide • Thermoregulation




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