Global Reach 2018: nitric oxide-mediated cutaneous vasodilation is reduced in chronic, but not acute, hypoxia independently of enzymatic superoxide formation

Geoff B. Coombs, John D. Akins, Jordan C. Patik, Gustavo A. Vizcardo-Galindo, Romulo Figueroa-Mujica, Michael M. Tymko, Benjamin S Stacey, Angelo Iannetelli, Damian M Bailey, Francisco C. Villafuerte, Philip N. Ainslie, R. Matthew Brothers

Research output: Contribution to journalArticlepeer-review

Abstract

We tested the hypotheses that 1) cutaneous microvascular function is impaired by acute normobaric and chronic hypobaric hypoxia and 2) that the superoxide free radical (via NADPH oxidase or xanthine oxidase) contributes to this impairment via nitric oxide (NO) scavenging. Local heating-induced cutaneous hyperemia (39°C) was measured in the forearm of 11 male lowlanders at sea level (SL) and following 14-18 days at high altitude (HA; 4340 m in Cerro de Pasco, Peru), and compared to 11 highlanders residing permanently at this elevation. Cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure) was not different during 39°C [control site: 73 (19) vs. 71 (18)%max; P=0.68] between normoxia and acute normobaric hypoxia (FIO2=0.125; equivalent to HA), respectively. At HA, CVC was reduced during 39°C in lowlanders compared to SL [control site: 54 (14) vs. 73 (19)%max; P<0.01] and was lower in Andean highlanders compared to lowlanders at HA [control site: 50 (24) vs. 54 (14)%max; P=0.02]. The NO contribution to vasodilation during 39°C (i.e., effect of NO synthase inhibition) was reduced in lowlanders at HA compared to SL [control site: 41 (11) vs 49 (10)%max; P=0.04] and in Andean highlanders compared to lowlanders at HA [control site: 32 (21) vs. 41 (11)%max; P=0.01]. Intradermal administration (cutaneous microdialysis) of the superoxide mimetic Tempol, inhibition of xanthine oxidase (via allopurinol), or NADPH oxidase (via apocynin) had no influence on cutaneous endothelium-dependent dilation during any of the conditions (all main effects of drug P>0.05). These results suggest that time at HA impairs NO-mediated cutaneous vasodilation independent of enzymatic superoxide formation.

Original languageEnglish
Pages (from-to)451-458
Number of pages8
JournalFree Radical Biology and Medicine
Volume172
Early online date12 Jun 2021
DOIs
Publication statusPublished - 20 Aug 2021

Keywords

  • Endothelial function
  • High altitude
  • Intradermal microdialysis
  • Skin blood flow

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