The Nitric Oxide Contribution to Reflex Cutaneous Vasodilation During Intradermal Microdialysis is Similar When Quantified Either Within or Between Sites
Authors: Wolf S. Tony , Greaney Jody L. , Stanhewicz Anna E. , Alexander Lacy M. , Kenney W. Larry 
Published: April 2020

Nitric oxide (NO) is an important component of the reflex cutaneous vasodilatory response during whole body heating (WBH). The NO contribution to reflex cutaneous vasodilation can be quantified via local intradermal microdialysis delivery of the endothelial NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME), either (1) within a single site by perfusing L‐NAME after a set rise in oral temperature (ΔTor) is reached, or (2) between two sites, one of which acts as a control while the other is perfused with L‐NAME throughout WBH. It is unclear, however, whether these two methods of quantifying the NO contribution to reflex cutaneous vasodilation yield similar results.PurposeTo compare the NO contribution to reflex cutaneous vasodilation when calculated either within a site or between two sites. We hypothesized that the NO contribution to reflex cutaneous vasodilation would be similar when quantified either within or between sites.MethodsRetrospective analysis of skin blood flow responses during whole‐body heat stress (water‐perfused suit) was performed for 11 young (22 ± 1 yr) and 48 middle‐aged/older (64 ± 5 yr) adults. Two intradermal microdialysis fibers placed in the ventral skin of the forearm were perfused with either lactated Ringer’s (control) or 20 mM L‐NAME during WBH. After ΔTor = 1°C was reached, mean body temperature was clamped and 20 mM L‐NAME was added to the control site until a post‐L‐NAME plateau was established. Red cell flux was measured continuously at each site (laser‐Doppler flowmetry) and cutaneous vascular conductance (CVC = flux/MAP) was expressed as a percentage of maximum (%CVCmax; 28mM sodium nitroprusside + 43°C). The NO contribution to reflex vasodilation was calculated in two ways for each subject: (1) as the difference in %CVCmax between the ΔTor = 1°C and post‐L‐NAME plateau within the control site, and (2) as the difference in %CVCmax between the control and L‐NAME sites at ΔTor = 1°C.ResultsWhen analyzed as a single group, there were no differences between methods of quantifying the NO contribution to reflex vasodilation (17.3 ± 1.6% vs. 21.7 ± 2.9%, p = 0.09). Similarly, there were no differences between methods when the young (26.1 ± 4.9% vs. 36.0 ± 8.5%, p = 0.20) and middle‐aged/older (15.2 ± 1.5% vs. 18.3 ± 2.9%, p = 0.26) groups were analyzed separately. Maximal CVC was similar between the young (1.85 ± 0.19) and middle‐aged/older (1.66 ± 0.14) groups (p = 0.53). There was a negative correlation between age and NO contribution (R2 = 0.42; p = 0.02) with no difference in slope (p = 0.46) or intercept (p = 0.18) between the two methods.ConclusionQuantification of the NO contribution to reflex cutaneous vasodilation yields similar results when calculated either within a site or between two sites. Importantly, the well‐documented age‐related reduction in the NO contribution to reflex vasodilation is evident regardless of the method used. These data suggest that either of these two methods are effective for quantifying the NO contribution to reflex cutaneous vasodilation, regardless of the magnitude of the overall vasodilatory response.Support or Funding InformationSupported by NIH T‐32 Grant #5T32AG049676‐03