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The nitric oxide dependence of cutaneous microvascular function to independent and combined hypoxic cold exposure

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journal contribution
posted on 08.09.2020, 10:41 by Josh ArnoldJosh Arnold, Alex LloydAlex Lloyd, Stephen BaileyStephen Bailey, Tomomi Fujimoto, Ryoko Matsukate, Masataka Takayanagi, Takeshi Nishiyasu, Naoto Fujii
Hypoxic modulation of nitric oxide (NO) production pathways in the cutaneous microvasculature and its interaction with cold-induced reflex vasoconstriction, independent of local cooling, has yet to be identified. This study assessed the contribution of NO to non-glabrous microvasculature perfusion during hypoxia and whole-body cooling with concomitant inhibition of NO synthase (NOS; via L-NAME) and the nitrite reductase, xanthine oxidase (via allopurinol), two primary sources of NO production. Thirteen volunteers were exposed to independent and combined cooling via water perfused suit (5ºC) and normobaric hypoxia (FiO2, 0.109 ± 0.002). Cutaneous vascular conductance (CVC) was assessed across four sites with intradermal microdialysis perfusion of 1) Lactated Ringers solution (control), 2) 20 mmol L-NAME 3) 10 µmol allopurinol, or 4) combined L-NAME/allopurinol. Effects and interactions were assessed via 4-way repeated measures ANOVA. Independently, L-NAME reduced (43%, p < 0.001), while allopurinol did not alter CVC (p = 0.5). Cooling decreased CVC (p = 0.001) and the reduction in CVC was consistent across perfusates (~30%, p = 0.9). Hypoxia increased CVC (16%, p = 0.01), with this effect abolished by L-NAME infusion (p = 0.04). Cold-induced vasoconstriction was blunted by hypoxia, yet importantly hypoxia increased CVC to a similar extent (39% at the Ringer site) irrespective of environmental temperature, thus no interaction was observed between cold and hypoxia (p = 0.1). L-NAME restored vasoconstriction during combined cold-hypoxia (p = 0.01). This investigation suggests that reflex cold-induced cutaneous vasoconstriction acts independently of NO suppression, while hypoxia-induced cutaneous vasodilatation is dependent on NOS derived NO production.

Funding

JSPS KAKENHI Grant Number 17H04753

History

School

  • Sport, Exercise and Health Sciences

Published in

Journal of Applied Physiology

Volume

129

Issue

4

Pages

947 - 956

Publisher

American Physiological Society

Version

AM (Accepted Manuscript)

Rights holder

© American Physiological Society

Publisher statement

This paper was accepted for publication in the journal Journal of Applied Physiology and the definitive published version is available at https://doi.org/10.1152/japplphysiol.00487.2020

Acceptance date

01/09/2020

Publication date

2020-09-03

Copyright date

2020

ISSN

8750-7587

eISSN

1522-1601

Language

en

Depositor

Dr Stephen Bailey Deposit date: 4 September 2020