A NO way to BOLD?: Dietary nitrate alters the hemodynamic response to visual stimulation

Aamand, Rasmus; Dalsgaard, Tage; Ho, Yi-Ching Lynn; Møller, Arne; Roepstorff, Andreas; Lund, Torben Ellegaard

doi:10.1016/j.neuroimage.2013.06.069

Cited by 49 publications

(41 citation statements)

References 47 publications

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“…In a complementary study on the same subjects, we observed that nitrate ingestion decreased the BOLD amplitude measured by fMRI (1). As the BOLD amplitude will decrease if local oxygen consumption is increased, all else being equal, and as the present study shows that nitrate does not change the CBF response to visual stimulation before AZ injection, one could speculate that nitrate increases the oxygen demand of the neurons.…”

Section: The Effect Of Nitrate On Az's Cbf Modulation During Visual Ssupporting

confidence: 64%

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Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation

Aamand

Dalsgaard

et al. 2014

Journal of Applied Physiology

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Aamand R, Ho YL, Dalsgaard T, Roepstorff A, Lund TE. Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation. J Appl Physiol 116: 267-273, 2014. First published December 12, 2013 doi:10.1152/japplphysiol.00797.2013The carbonic anhydrase (CA) inhibitor acetazolamide (AZ) is used routinely to estimate cerebrovascular reserve capacity in patients, as it reliably increases cerebral blood flow (CBF). However, the mechanism by which AZ accomplishes this CBF increase is not entirely understood. We recently discovered that CA can produce nitric oxide (NO) from nitrite, and that AZ enhances this NO production in vitro. In fact, this interaction between AZ and CA accounted for a large part of AZ's vasodilatory action, which fits well with the known vasodilatory potency of NO. The present study aimed to assess whether AZ acts similarly in vivo in the human cerebrovascular system. Hence, we increased or minimized the dietary intake of nitrate in 20 healthy male participants, showed them a full-field flickering dartboard, and measured their CBF response to this visual stimulus with arterial spin labeling. Doing so, we found a significant positive interaction between the dietary intake of nitrate and the CBF modulation afforded by AZ during visual stimulation. In addition, but contrary to studies conducted in elderly participants, we report no effect of nitrate intake on resting CBF in healthy human participants. The present study provides in vivo support for an enhancing effect of AZ on the NO production from nitrite catalyzed by CA in the cerebrovascular system. Furthermore, our results, in combination with the results of other groups, indicate that nitrate may have significant importance to vascular function when the cerebrovascular system is challenged by age or disease.nitrate; cerebral blood flow; nitric oxide; acetazolamide ACETAZOLAMIDE (AZ) IS WELL known to increase cerebral blood flow (CBF) and is used routinely to estimate cerebrovascular reserve capacity (CVRC) in patients (13, 32). However, the mechanism by which AZ accomplishes this CBF increase is not entirely understood (35). AZ is an inhibitor of the ubiquitous enzyme carbonic anhydrase (CA), which normally catalyzes the reversible hydration of CO 2 (CO 2 ϩ H 2 O ↔ H 2 CO 3 ↔ HCO 3 Ϫ ϩ H ϩ ). CA is thus an integral part of the system that rids the body of the CO 2 produced in tissues (26). For the same reason, CA also acts to equilibrate the pH transients occurring, e.g., upon metabolic activity. The effect of AZ is usually assumed to be linked to cerebral acidosis caused by an AZ-induced increase in the cerebral partial pressure of CO 2 (PCO 2 ) (5).We recently discovered that CA is also capable of catalyzing the conversion of the endogenous anion nitrite into nitric oxide (NO) (2), a potent vasodilator. In that study, we also attempted to block CA's catalyzation of the NO production by introducing the CA inhibitor AZ to the reaction. However, to our surprise, AZ markedly increased the production of NO ...

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Section: The Effect Of Nitrate On Az's Cbf Modulation During Visual Ssupporting

confidence: 64%

“…Participants had to press a button each time this happened to indicate that they attended to the stimulus. Further details on stimulus delivery can be found in our complementary paper (1).…”

Section: Stimuli Deliverymentioning

confidence: 99%

Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation

Aamand

Dalsgaard

et al. 2014

Journal of Applied Physiology

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“…Similar to the serial 3s subtraction task, the Stroop task assesses the capacity for information processing (Besner and Roberts 2005) and performance in these tasks is related to the functioning of the prefrontal cortex. NO is pivotal to a number of cerebral processes including neurotransmission, vasodilation and neurovascular coupling (Aamand et al 2013;Iadecola et al 1999;Piknova et al 2011;Rifkind et al 2007). Dietary NO 3 -has been shown to improve regional brain perfusion (Presley et al 2011), attenuate cerebral O 2 extraction during mental processing (Thompson et al 2014), and enhance coupling of cerebral blood flow to neuronal activity (Aamand et al 2013).…”

Section: The Effect Of Br On Cognitive Performance At Restmentioning

confidence: 99%

“…NO is pivotal to a number of cerebral processes including neurotransmission, vasodilation and neurovascular coupling (Aamand et al 2013;Iadecola et al 1999;Piknova et al 2011;Rifkind et al 2007). Dietary NO 3 -has been shown to improve regional brain perfusion (Presley et al 2011), attenuate cerebral O 2 extraction during mental processing (Thompson et al 2014), and enhance coupling of cerebral blood flow to neuronal activity (Aamand et al 2013). Therefore, the modulation of cerebral haemodynamics, especially in response to cognitive task performance (Wightman et al 2015), may underpin the differences in response time between BR and PL in the present study.…”

Section: The Effect Of Br On Cognitive Performance At Restmentioning

confidence: 99%

Dietary Nitrate Supplementation Improves Sprint and High-Intensity Intermittent Running Performance

Thompson

Vanhatalo

Jell

et al. 2017

Medicine &Amp; Science in Sports &Amp; Exercise

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“…Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, Piknova et al found that nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude [57]. In subjects with elevated dietary nitrate, a faster and smaller MRI-BOLD response, with less variation across local cortex, was observed which is consistent with an enhanced hemodynamic coupling [58]. Wightman et al found that single doses of dietary nitrate could modulate the CBF response to cognitive task performance and potentially improve performance [59].…”

Section: Nitrite and Neurovascular Couplingmentioning

confidence: 96%

Inorganic Nitrite as a Potential Therapy or Biomarker for Concussion

Silver¹

2016

J Neurol Neurophysiol

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One of the hallmarks of concussion is a disturbance, typically a reduction, in cerebral blood flow. Studies have shown a rapid increase in nitric oxide within minutes following head injury, followed by a decline to below baseline within hours. This reduction in nitrite levels is closely linked to a reduction in cerebral blood flow. Inorganic nitrite has recently been shown to be a source of nitric oxide under conditions of ischemia or hypoxia, and has been shown to increase cerebral blood flow and to improve neurovascular coupling. Dietary nitrate has been shown to be converted to nitrite in the bloodstream. This review suggests that inorganic nitrite, and/or dietary nitrate, should be investigated for their potential in treating concussion symptoms.

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A NO way to BOLD?: Dietary nitrate alters the hemodynamic response to visual stimulation

Cited by 49 publications

References 47 publications

Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation

Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation

Dietary Nitrate Supplementation Improves Sprint and High-Intensity Intermittent Running Performance

Inorganic Nitrite as a Potential Therapy or Biomarker for Concussion

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