Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia

Wesley K. Lefferts, William E. Hughes, Corey N. White, Tom D. Brutsaert, Kevin S. Heffernan

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ±0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensori-motor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6±1.0 arbitrary units (AU)) compared with PLA (+0.2±0.3AU; p<0.05). Memory performance (−6±13 correct) significantly decreased (p<0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p>0.05). MCA flow increased during Stroop similarly in normoxia (PLA+5±6cm·s−1, NIT+7±7cm·s−1) and hypoxia (PLA+5±9cm·s−1, NIT+6±7cm·s−1) (p<0.05) and this increase was not altered by PLA or NIT (p>0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalApplied Physiology, Nutrition and Metabolism
Issue number2
StatePublished - Oct 26 2015


  • Cognition
  • Hypoxia
  • Neurovascular coupling
  • Nitrate

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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