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


Journal

Nitric oxide : biology and chemistry
ISSN: 1089-8611
Titre abrégé: Nitric Oxide
Pays: United States
ID NLM: 9709307

Informations de publication

Date de publication:
01 01 2020
Historique:
received: 04 07 2019
revised: 28 08 2019
accepted: 07 10 2019
pubmed: 12 10 2019
medline: 22 12 2020
entrez: 12 10 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31604146
pii: S1089-8603(19)30207-1
doi: 10.1016/j.niox.2019.10.004
pmc: PMC6970220
pii:
doi:

Substances chimiques

Nitrates 0
Nitrites 0
Nitroso Compounds 0

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

27-35

Subventions

Organisme : Medical Research Council
ID : G0701115
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P008887/1
Pays : United Kingdom

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Références

Pharmacol Res. 2017 Aug;122:127-129
pubmed: 28610958
J Appl Physiol (1985). 1991 May;70(5):1938-42
pubmed: 1864773
Nitric Oxide. 2016 Sep 30;59:63-70
pubmed: 27553127
Crit Care. 2007;11(5):R101
pubmed: 17845716
Extrem Physiol Med. 2015 Jun 09;4:8
pubmed: 26060573
J Appl Physiol (1985). 2017 Oct 1;123(4):983-992
pubmed: 28684588
Contemp Clin Trials. 2013 Nov;36(2):450-9
pubmed: 24028941
J Appl Physiol (1985). 1986 May;60(5):1734-42
pubmed: 3710990
Nitric Oxide. 2017 Sep 30;69:1-9
pubmed: 28684191
Nitric Oxide. 2016 Nov 30;60:24-31
pubmed: 27593617
High Alt Med Biol. 2018 Mar;19(1):21-27
pubmed: 29211505
Pharmacol Ther. 2014 Dec;144(3):303-20
pubmed: 24992304
Crit Care Med. 1999 Jul;27(7):1369-77
pubmed: 10446833
Am J Phys Anthropol. 1998 Jul;106(3):385-400
pubmed: 9696153
J Physiol. 2013 Jan 15;591(2):547-57
pubmed: 23070702
J Biol Chem. 2008 Dec 5;283(49):33927-34
pubmed: 18835812
Front Physiol. 2015 Oct 14;6:288
pubmed: 26528189
Nat Rev Drug Discov. 2008 Feb;7(2):156-67
pubmed: 18167491
PLoS One. 2015 Mar 05;10(3):e0118730
pubmed: 25742500
Am J Physiol Regul Integr Comp Physiol. 2010 Oct;299(4):R1121-31
pubmed: 20702806
Annu Rev Nutr. 2018 Aug 21;38:303-328
pubmed: 30130468
Nat Rev Neurosci. 2013 May;14(5):365-76
pubmed: 23571845
Am J Physiol Heart Circ Physiol. 2015 Nov;309(9):H1419-39
pubmed: 26320036
Acta Physiol (Oxf). 2007 Sep;191(1):59-66
pubmed: 17635415
Acta Anaesthesiol Scand. 2015 Nov;59(10):1246-59
pubmed: 26149711
Sci Rep. 2011;1:109
pubmed: 22355626
Front Physiol. 2017 Jun 09;8:401
pubmed: 28649204
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17593-8
pubmed: 17971439
Wilderness Environ Med. 2015 Mar;26(1):4-10
pubmed: 25435349
N Engl J Med. 2009 Jan 8;360(2):140-9
pubmed: 19129527
Circ Res. 2009 Mar 27;104(6):796-804
pubmed: 19229060
J Appl Physiol (1985). 2017 Apr 1;122(4):1011-1018
pubmed: 28126908
Am J Clin Nutr. 2018 Dec 1;108(6):1353-1354
pubmed: 30379994
Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F378-F387
pubmed: 28490529
Am J Phys Anthropol. 1984 Mar;63(3):301-6
pubmed: 6731601
BMC Med Res Methodol. 2010 Oct 21;10:98
pubmed: 20964858
J Appl Physiol (1985). 2019 Oct 1;127(4):1012-1033
pubmed: 31095460
Nitric Oxide. 2017 Dec 1;71:57-68
pubmed: 29042272
Cardiovasc Res. 2020 Jan 1;116(1):51-62
pubmed: 31372656
Med Sci Sports Exerc. 2014 Jan;46(1):143-50
pubmed: 23846159
Am J Clin Nutr. 2018 Jun 1;107(6):894-908
pubmed: 29868911
FASEB J. 2002 Nov;16(13):1775-85
pubmed: 12409320
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11459-64
pubmed: 20534544
Pharmacol Rev. 1991 Jun;43(2):109-42
pubmed: 1852778
Exp Physiol. 2010 Aug;95(8):880-91
pubmed: 20418348
Extrem Physiol Med. 2015 Feb 26;4:2
pubmed: 25722851
Opt Express. 2007 Nov 12;15(23):15101-14
pubmed: 19550794
Physiology (Bethesda). 2014 Nov;29(6):388-402
pubmed: 25362633
BMJ. 2011 Aug 15;343:d4943
pubmed: 21844157
Eur J Appl Physiol. 2009 Jun;106(3):473-8
pubmed: 19333616
Antioxid Redox Signal. 2017 Oct 1;27(10):684-712
pubmed: 28398072
Gut. 1997 Feb;40(2):211-4
pubmed: 9071933

Auteurs

Andrew F Cumpstey (AF)

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.

Philip J Hennis (PJ)

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.

Edward T Gilbert-Kawai (ET)

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.

Bernadette O Fernandez (BO)

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.

Daniel Grant (D)

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.

William Jenner (W)

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.

Matthieu Poudevigne (M)

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.

Helen Moyses (H)

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.

Denny Zh Levett (DZ)

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.

Alexandra Cobb (A)

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.

Paula Meale (P)

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.

Kay Mitchell (K)

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.

Helmut Pöhnl (H)

AURAPA, Paul-Heidelbauer-Straße 26, 74321, Bietigheim-Bissingen, Germany.

Monty G Mythen (MG)

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.

Michael Pw Grocott (MP)

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.

Daniel S Martin (DS)

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.

Martin Feelisch (M)

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.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH