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Nitric Oxide. 2019 Oct 8;94:27-35. doi: 10.1016/j.niox.2019.10.004. [Epub ahead of print]

Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - A randomised controlled trial (Xtreme Alps).

Author information

1
Critical Care Research Area, Southampton, NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK.
2
UCL Centre for Altitude, Space and Extreme Environment (CASE) Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport Exercise & Health, 170 Tottenham Court Road, London, W1T 7HA, UK.
3
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK; Warwick Medical School, Division of Metabolic and Vascular Health, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
4
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.
5
AURAPA, Paul-Heidelbauer-Straße 26, 74321, Bietigheim-Bissingen, Germany.
6
UCL Centre for Altitude, Space and Extreme Environment (CASE) Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport Exercise & Health, 170 Tottenham Court Road, London, W1T 7HA, UK. Electronic address: daniel.martin@ucl.ac.uk.
7
Critical Care Research Area, Southampton, NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK; Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK; Warwick Medical School, Division of Metabolic and Vascular Health, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. Electronic address: m.feelisch@soton.ac.uk.

Abstract

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 μM) and at day 5 (D5) of high altitude (22.9 vs 84.3 μM, p < 0.001). Dietary nitrate supplementation also significantly increased both plasma nitrite (0.78 vs. 0.86 μM SL, 0.31 vs. 0.41 μM D5, p = 0.03) and total nitroso product (11.3 vs. 19.7 nM SL, 9.7 vs. 12.3 nM D5, p < 0.001) levels both at sea level and at 4559 m. However, plasma nitrite concentrations were more than 50% lower at 4559 m compared to sea level in both treatment groups. Despite these significant changes, dietary nitrate supplementation had no effect on any measured read-outs of sublingual or forearm blood flow, even when environmental hypoxia was experimentally reversed using supplemental oxygen. In conclusion, dietary nitrate supplementation does not improve microcirculatory function at 4559 m.

KEYWORDS:

Altitude; Hypoxia; Microcirculation; Nitrate; Nitric oxide; Nitrite

PMID:
31604146
DOI:
10.1016/j.niox.2019.10.004
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