Oral Nitrate Supplementation Differentially Modulates Cerebral Artery Blood Velocity and Prefrontal Tissue Oxygenation During 15 km Time-Trial Cycling in Normoxia but Not in Hypoxia.

Jui-Lin Fan,Philippe Meyer,Bengt Kayser,Nicolas Bourdillon

doi:10.3389/fphys.2018.00869

Abstract

Background: Nitrate is a precursor of nitric oxide (NO), an important regulator of cerebral perfusion in normoxic and hypoxic conditions. Nitrate supplementation could be used to improve cerebral perfusion and oxygenation during exercise in hypoxia. The effects of dietary nitrate supplementation on cerebral haemodynamics during exercise in severe hypoxia (arterial O2 saturation < 70%) have not been explored.Methods: In twelve trained male cyclists, we measured blood pressure (BP), middle cerebral artery blood velocity (MCAv), cerebrovascular resistance (CVR) and prefrontal oxyhaemoglobin and deoxyhaemoglobin concentration (O2Hb and HHb, respectively) during 15 km cycling time trials (TT) in normoxia and severe hypoxia (11% inspired O2, peripheral O2 saturation ∼66%) following 3-day oral supplementation with placebo or sodium nitrate (0.1 mmol/kg/day) in a randomised, double-blinded manner. We tested the hypothesis that dietary nitrate supplementation increases MCAv and cerebral O2Hb during TT in severe hypoxia.Results: During TT in normoxia, nitrate supplementation lowered MCAv by ∼2.3 cm/s and increased cerebral O2Hb by ∼6.8 μM and HHb by ∼2.1 μM compared to normoxia placebo (p ≤ 0.01 for all), while BP tended to be lowered (p = 0.06). During TT in severe hypoxia, nitrate supplementation elevated MCAv (by ∼2.5 cm/s) and BP (by ∼5 mmHg) compared to hypoxia placebo (p < 0.01 for both), while it had no effect on cerebral O2Hb (p = 0.98), HHb (p = 0.07) or PETCO2 (p = 0.12). Dietary nitrate had no effect of CVR during TT in normoxia or hypoxia (p = 0.19).Conclusion: Our findings indicate that during normoxic TT, the modulatory effect of dietary nitrate on regional and global cerebral perfusion is heterogeneous. Meanwhile, the lack of major changes in cerebral perfusion with dietary nitrate during hypoxic TT alludes to an exhausted cerebrovascular reserve.

Highlights

MATERIALS AND METHODSNitric oxide (NO) is an important signalling molecule, responsible for regulating blood flow and tissue oxygen (O2) delivery under hypoxic conditions (Ignarro, 1989a,b; Kulandavelu et al, 2015)
Dietary nitrate tended to have a greater effect on mean blood pressure (BP) in hypoxia compared to normoxia, while no treatment effect was observed in any other cardiorespiratory variables (Table 1)
Post hoc analysis showed a trend for higher resting BP with dietary nitrate in hypoxia compared to hypoxic placebo value, while no such differences were observed in normoxia (d = 0.2, p = 0.51)

Summary

Introduction

Nitric oxide (NO) is an important signalling molecule, responsible for regulating blood flow and tissue oxygen (O2) delivery under hypoxic conditions (Ignarro, 1989a,b; Kulandavelu et al, 2015). We found cerebral O2 delivery and prefrontal cortex tissue oxygenation to be reduced during exercise in severe hypoxia despite elevated middle cerebral artery blood velocity (MCAv) (Fan et al, 2013). Understanding the role of NO in the regulation CBF during exercise in normoxic and severe hypoxic conditions could provide novel insights into the compensatory mechanism(s) by which the cerebral O2 supply is maintained. Nitrate is a precursor of nitric oxide (NO), an important regulator of cerebral perfusion in normoxic and hypoxic conditions. The effects of dietary nitrate supplementation on cerebral haemodynamics during exercise in severe hypoxia (arterial O2 saturation < 70%) have not been explored

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