Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults

Overview

Journal Nitric Oxide

Publisher Elsevier

Date 2010 Oct 19

PMID 20951824

Citations 99

Authors

Tennille D Presley

Ashley R Morgan

Erika Bechtold

William Clodfelter

Robin W Dove

Janine M Jennings

Robert A Kraft

S Bruce King

Paul J Laurienti

W Jack Rejeski

Jonathan H Burdette

Daniel B Kim-Shapiro

Gary D Miller

Affiliations

Soon will be listed here.

Abstract

Aims: Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults.

Methods And Results: In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex.

Conclusion: These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

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References

Gates P, Boucher M, Silver A, Monahan K, Seals D . Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression. J Appl Physiol (1985). 2006; 102(1):63-71. DOI: 10.1152/japplphysiol.00660.2006. View

Kozlov A, Costantino G, Sobhian B, Szalay L, Umar F, Nohl H . Mechanisms of vasodilatation induced by nitrite instillation in intestinal lumen: possible role of hemoglobin. Antioxid Redox Signal. 2005; 7(3-4):515-21. DOI: 10.1089/ars.2005.7.515. View

Rifkind J, Nagababu E, Barbiro-Michaely E, Ramasamy S, Pluta R, Mayevsky A . Nitrite infusion increases cerebral blood flow and decreases mean arterial blood pressure in rats: a role for red cell NO. Nitric Oxide. 2007; 16(4):448-56. DOI: 10.1016/j.niox.2007.04.002. View

Shiva S, Huang Z, Grubina R, Sun J, Ringwood L, MacArthur P . Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res. 2007; 100(5):654-61. DOI: 10.1161/01.RES.0000260171.52224.6b. View

Govoni M, Jansson E, Weitzberg E, Lundberg J . The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008; 19(4):333-7. DOI: 10.1016/j.niox.2008.08.003. View

Holland C, Smith E, Csapo I, Gurol M, Brylka D, Killiany R . Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke. 2008; 39(4):1127-33. PMC: 2754400. DOI: 10.1161/STROKEAHA.107.497438. View

Zweier J, Wang P, Samouilov A, Kuppusamy P . Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995; 1(8):804-9. DOI: 10.1038/nm0895-804. View

MILLAR T, Stevens C, Benjamin N, Eisenthal R, Harrison R, Blake D . Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Lett. 1998; 427(2):225-8. DOI: 10.1016/s0014-5793(98)00430-x. View

Oosterman J, van Harten B, Weinstein H, Scheltens P, Sergeant J, Scherder E . White matter hyperintensities and working memory: an explorative study. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2008; 15(3):384-99. DOI: 10.1080/13825580701879998. View

10.

Li H, Kundu T, Zweier J . Characterization of the magnitude and mechanism of aldehyde oxidase-mediated nitric oxide production from nitrite. J Biol Chem. 2009; 284(49):33850-8. PMC: 2797155. DOI: 10.1074/jbc.M109.019125. View

11.

Avery A . Infantile methemoglobinemia: reexamining the role of drinking water nitrates. Environ Health Perspect. 1999; 107(7):583-6. PMC: 1566680. DOI: 10.1289/ehp.99107583. View

12.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

13.

Lundberg J, Weitzberg E, Gladwin M . The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008; 7(2):156-67. DOI: 10.1038/nrd2466. View

14.

Spilt A, Weverling-Rijnsburger A, Middelkoop H, van der Flier W, Gussekloo J, de Craen A . Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology. 2005; 236(3):990-5. DOI: 10.1148/radiol.2363041454. View

15.

Yang Y, Frank J, Hou L, Ye F, Mclaughlin A, Duyn J . Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling. Magn Reson Med. 1998; 39(5):825-32. DOI: 10.1002/mrm.1910390520. View

16.

Kim-Shapiro D, Gladwin M, Patel R, Hogg N . The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation. J Inorg Biochem. 2004; 99(1):237-46. DOI: 10.1016/j.jinorgbio.2004.10.034. View

17.

Basu S, Azarova N, Font M, King S, Hogg N, Gladwin M . Nitrite reductase activity of cytochrome c. J Biol Chem. 2008; 283(47):32590-7. PMC: 2583304. DOI: 10.1074/jbc.M806934200. View

18.

Castello P, David P, McClure T, Crook Z, Poyton R . Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes. Cell Metab. 2006; 3(4):277-87. DOI: 10.1016/j.cmet.2006.02.011. View

19.

Nordahl C, Ranganath C, Yonelinas A, DeCarli C, Fletcher E, Jagust W . White matter changes compromise prefrontal cortex function in healthy elderly individuals. J Cogn Neurosci. 2006; 18(3):418-29. PMC: 3776596. DOI: 10.1162/089892906775990552. View

20.

Webb A, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S . Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. 2008; 51(3):784-90. PMC: 2839282. DOI: 10.1161/HYPERTENSIONAHA.107.103523. View