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J Appl Physiol (1985). 2019 Jul 18. doi: 10.1152/japplphysiol.01116.2018. [Epub ahead of print]

Dietary nitrate supplementation enhances cerebrovascular CO2 reactivity in a sex-specific manner.

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Department of Surgery & Anaesthesia, University of Otago, New Zealand.
Department of Surgery & Anaethesia, University of Otago, New Zealand.
Paediatrics & Child Health, University of Otago (Wellington), New Zealand.
School of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Western Australia, Australia.


Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and increased NO has the potential to enhance cerebral blood flow (CBF). Dietary supplementation with sodium nitrate, a precursor of NO, could improve cerebrovascular function but this has not been investigated. In seventeen individuals, we examined the effects of a 7-day supplementation of dietary nitrate (0.1mmol/kg/day) on cerebrovascular function using a randomised, single-blinded placebo-controlled crossover design. We hypothesized that 7-day dietary nitrate supplementation increases CBF response to CO2 (cerebrovascular CO2 reactivity) and cerebral autoregulation (CA). We assessed middle cerebral artery blood velocity (MCAv) and blood pressure (BP) at rest and during CO2 breathing. Transfer function analysis was performed on resting beat-to-beat MCAv and BP to determine CA, from which phase, gain and coherence of the BP-MCAv data were derived. Dietary nitrate elevated plasma nitrate concentration by ˜420% (P<0.001) and lowered gain (d = 1.2, P = 0.025) and phase of the BP-MCAv signal compared to placebo treatment (d=0.7, P=0.043), while coherence was unaffected (P=0.122). Dietary nitrate increased the MCAv-CO2 slope in a sex-specific manner (interaction: P=0.016). Dietary nitrate increased the MCAv-CO2 slope in males (d=1.0, P=0.014 vs. placebo), but had no effect in females (P=0.919). Our data demonstrate that dietary nitrate greatly increased cerebrovascular CO2 reactivity in healthy individuals, while its effect on CA remains unclear. The selective increase in the MCAv-CO2 slope observed in males indicates a clear sexual dimorphic role of NO in cerebrovascular function.


cerebral CO2 reactivity; cerebral blood flow; cerebrovascular autoregulation; dietary nitrate supplementation; nitric oxide

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