title: A NO way to BOLD? Dietary nitrate alters the hemodynamic response to visual stimulation.
abstract: Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual stimuli based on the retinotopic characteristics of the visual cortex. Our primary measure of the hemodynamic response was the blood oxygenation level dependent (BOLD) response measured with high-resolution functional magnetic resonance imaging (0.64×0.64×1.8 mm) in the visual cortex. From this response, we made a direct estimate of key parameters characterizing the shape of the BOLD response (i.e. lag and amplitude). During elevated nitrate intake, corresponding to the nitrate content of a large plate of salad, both the hemodynamic lag and the BOLD amplitude decreased significantly (7.0±2% and 7.9±4%, respectively), and the variation across activated voxels of both measures decreased (12.3±4% and 15.3±7%, respectively). The baseline cerebral blood flow was not affected by nitrate. Our experiments demonstrate, for the first time, that dietary nitrate may modulate the local cerebral hemodynamic response to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties of neurovascular coupling. This could have major clinical implications, which remain to be explored.
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Denmark; Department of Bioscience, Aarhus University, Denmark. Electronic address: rasmus.aamand@cfin.au.dk.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Aamand
authors.forename: Thomas
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Yi-Ching Lynn
authors.initials: YC
authors.lastname: Ho
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.forename: Andreas
authors.initials: A
authors.lastname: Roepstorff
authors.forename: Torben E
authors.initials: TE
authors.lastname: Lund
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009566:Nitrates / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods*; D015990:Placebo Effect; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014796:Visual Perception / Q000502:physiology*
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide
keywords: BOLD amplitude; CS; Cerebral blood flow; Hemodynamic lag; M; MAD; MeanAD; NO; NO synthase; NOS; Nitrate; Nitric oxide; P/O ratio; calcarine sulcus; mean absolute deviation; median absolute deviation; metHb; methemoglobin; nitric oxide; oxidative phosphorylation efficiency; p2p; peak-to-peak amplitude; voxel-wise estimate of BOLD amplitude; voxel-wise estimate of hemodynamic lag; τ