Dietary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deficient mice
Open accessAbstract
Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the stepwise oxidation of NO and have, for years, been regarded as inactive degradation products. As a result, both anions are routinely used as surrogate markers of NO production, with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady-state concentrations of NO metabolites thought to originate from nitric oxide synthase (NOS)-derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS-/-) demonstrated decreased blood and tissue nitrite, nitrate, and nitroso proteins, which were further reduced by low-nitrite (NOx) diet for 1 week. Nitrite supplementation (50 mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS-/- mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The nitrate/nitrite content of fruits and vegetables could contribute to their cardiovascular health benefits in animals and humans.
“the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals [29,33,78,79,80,81,82,83] and humans [31,84,85,86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [82]
Pretreatment with sodium nitrite protects against ischemia/reperfusion injury in the heart in preclinical models.
“pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [20]
In vivo administration of nitrite via direct infusion, dietary supplementation, or its two-electron oxidized precursor nitrate leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation.
“in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [85]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,745 · see citing works
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 1× · see citing works
“confounding effects of nitrite and nitrate acting as NOS-independent sources of NO [9].”
BackgroundHypertension in mice lacking the gene for endothelial nitric oxide synthase
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C. (1995) · Nature · doi:10.1038/377239a0 · Cited by 2,070 · see citing works
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807 · see citing works
Arnold, W. P., Mittal, C. K., Katsuki, S., & Murad, F. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.8.3203 · Cited by 1,459 · see citing works
Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078 · see citing works
Elevated blood pressures in mice lacking endothelial nitric oxide synthase
Shesely, E. G., Maeda, N., Kim, H.-S., Desai, K. M., Krege, J. H., Laubach, V. E., Sherman, P. A., Sessa, W. C., & Smithies, O. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13176 · Cited by 914 · see citing works
Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs
Ward, M. H., de Kok, T. M. C. M., Levallois, P., Brender, J. D., Guliš, G., Nolan, B. T., & VanDerslice, J. A. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8043 · Cited by 892 · see citing works
Nitric Oxide: Pathophysiological Mechanisms
Gross, S. S., & Wolin, M. S. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003513 · Cited by 888 · see citing works
Enzyme-independent formation of nitric oxide in biological tissues
Zweier, J. L., Wang, P., Samouilov, A., & Kuppusamy, P. (1995) · Nature Medicine · doi:10.1038/nm0895-804 · Cited by 788 · see citing works
Duncan, C., Dougall, H., Johnston, P., Green, S., Brogan, R., Leifert, C., Smith, L., Golden, M., & Benjamin, N. (1995) · Nature Medicine · doi:10.1038/nm0695-546 · Cited by 734 · see citing works
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674 · cited 1× · see citing works
“Surgical procedures used in themyocardial I/R protocol were similar to methods described previously [22,23].”
MethodBenjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665 · see citing works
Inorganic nitrate is a possible source for systemic generation of nitric oxide
Lundberg, J. O., & Govoni, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.027 · Cited by 657 · see citing works
Furchgott, R. F., & Bhadrakom, S. (1953) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)05163-8 · Cited by 655 · cited 1× · see citing works
“As early as 1880, nitrite was described in terms of its vasodilatory abilities [50], and much later, Furchgott and Bhadrakom used acidified sodium nitrite to relax precontracted aortic strips in 1953 [51].”
BackgroundEffects of dietary nitrate on oxygen cost during exercise
Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01713.x · Cited by 637 · see citing works
Webb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · cited 1× · see citing works
“There are many systems shown to be capable of reducing nitrite to NO including mitochondrial electron transport system [37–41], simple protonation [42,43], deoxyhemoglobin [25,43], deoxymyoglobin [44] and xanthine oxidase [45–47].”
BackgroundEffects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
Larsen, F. J., Ekblom, B., Sahlin, K., Lundberg, J. O., & Weitzberg, E. (2006) · New England Journal of Medicine · doi:10.1056/nejmc062800 · Cited by 587 · see citing works
Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals
Kleinbongard, P., Dejam, A., Lauer, T., Rassaf, T., Schindler, A., Picker, O., Scheeren, T., Gödecke, A., Schrader, J., Schulz, R., et al. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00406-4 · Cited by 586 · see citing works
Self-citationLauer, T., Preik, M., Rassaf, T., Strauer, B. E., Deussen, A., Feelisch, M., & Kelm, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221381098 · Cited by 585 · see citing works
Shiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555 · see citing works
Self-citationNitrite is a signaling molecule and regulator of gene expression in mammalian tissues
Bryan, N. S., Fernandez, B. O., Bauer, S. M., Garcia-Saura, M. F., Milsom, A. B., Rassaf, T., Maloney, R. E., Bharti, A., Rodriguez, J., & Feelisch, M. (2005) · Nature Chemical Biology · doi:10.1038/nchembio734 · Cited by 518 · see citing works
Self-citationRelevance of nitrosamines to human cancer
Bartsch, H., & Montesano, R. (1984) · Carcinogenesis · doi:10.1093/carcin/5.11.1381 · Cited by 495 · see citing works
Feelisch, M., Rassaf, T., Mnaimneh, S., Singh, N., Bryan, N. S., Jourd'Heuil, D., & Kelm, M. (2002) · The FASEB Journal · doi:10.1096/fj.02-0363com · Cited by 401 · see citing works
Bryan, N. S., Rassaf, T., Maloney, R. E., Rodriguez, C. M., Saijo, F., Rodriguez, J. R., & Feelisch, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306706101 · Cited by 400 · see citing works
Self-citationDietary nitrite supplementation protects against myocardial ischemia-reperfusion injury
Bryan, N. S., Calvert, J. W., Elrod, J. W., Gundewar, S., Ji, S. Y., & Lefer, D. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706579104 · Cited by 347 · see citing works
Self-citationNitrite reductase activity is a novel function of mammalian mitochondria
Kozlov, A. V., Staniek, K., & Nohl, H. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00788-7 · Cited by 342 · cited 1× · see citing works
“There are many systems shown to be capable of reducing nitrite to NO including mitochondrial electron transport system [37–41], simple protonation [42,43], deoxyhemoglobin [25,43], deoxymyoglobin [44] and xanthine oxidase [45–47].”
BackgroundNitric Oxide in Vascular Biology
Walford, G., & Loscalzo, J. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00345.x · Cited by 302 · see citing works
Rassaf, T., Flögel, U., Drexhage, C., Hendgen-Cotta, U., Kelm, M., & Schrader, J. (2007) · Circulation Research · doi:10.1161/circresaha.107.152488 · Cited by 284 · see citing works
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator
Hunter, C. J., Dejam, A., Blood, A. B., Shields, H., Kim-Shapiro, D. B., Machado, R. F., Tarekegn, S., Mulla, N., Hopper, A. O., Schechter, A. N., et al. (2004) · Nature Medicine · doi:10.1038/nm1109 · Cited by 281 · see citing works
Jones, S. P., Girod, W. G., Palazzo, A. J., Granger, D. N., Grisham, M. B., Jourd’heuil, D., Huang, P. L., & Lefer, D. J. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.276.5.h1567 · Cited by 265 · see citing works
Coronary Hemodynamics in Endothelial NO Synthase Knockout Mice
Gödecke, A., Decking, U. K. M., Ding, Z., Hirchenhain, J., Bidmon, H. J., Gödecke, S., & Schrader, J. (1998) · Circulation Research · doi:10.1161/01.res.82.2.186 · Cited by 263 · see citing works
Nitrite in saliva increases gastric mucosal blood flow and mucus thickness
Björne, H., Petersson, J., Phillipson, M., Weitzberg, E., Holm, L., & Lundberg, J. O. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19019 · Cited by 246 · see citing works
Hypoxic Modulation of Exogenous Nitrite-Induced Vasodilation in Humans
Maher, A. R., Milsom, A. B., Gunaruwan, P., Abozguia, K., Ahmed, I., Weaver, R. A., Thomas, P., Ashrafian, H., Born, G. V. R., James, P. E., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.719591 · Cited by 210 · see citing works
Sun, D., Huang, A., Smith, C. J., Stackpole, C. J., Connetta, J. A., Shesely, E. G., Koller, A., & Kaley, G. (1999) · Circulation Research · doi:10.1161/01.res.85.3.288 · Cited by 186 · see citing works
Tischner, R., Planchet, É., & Kaiser, W. M. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.09.004 · Cited by 170 · see citing works
Nitric oxide synthase reduces nitrite to NO under anoxia
Vanin, A. F., Bevers, L. M., Slama-Schwok, A., & van Faassen, E. E. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6374-2 · Cited by 151 · see citing works
Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314336200 · Cited by 146 · see citing works
Cardiovascular and renal control in NOS-deficient mouse models
Ortiz, P. A., & Garvin, J. L. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00401.2002 · Cited by 131 · see citing works
Waldron, G. J., Ding, H., Lovren, F., Kubes, P., & Triggle, C. R. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702858 · Cited by 128 · see citing works
Nitrite is an alternative source of NO in vivo
Tsuchiya, K., Kanematsu, Y., Yoshizumi, M., Ohnishi, H., Kirima, K., Izawa, Y., Shikishima, M., Ishida, T., Kondo, S., Kagami, S., et al. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00525.2004 · Cited by 127 · see citing works
Enzymology of Nitric Oxide Synthases
Hemmens, B., & Mayer, B. (2003) · Humana Press eBooks · doi:10.1385/1-59259-749-1:1 · Cited by 119 · see citing works
NO-synthase and nitrite-reductase components of nitric oxide cycle.
Reutov, V. P., & Sorokina, E. G. (1998) · PubMed · Cited by 118 · see citing works
Mitochondria recycle nitrite back to the bioregulator nitric monoxide.
Nohl, H., Staniek, K., Sobhian, B., Bahrami, S., Redl, H., & Kozlov, A. V. (2000) · Acta Biochimica Polonica · doi:10.18388/abp.2000_3946 · Cited by 116 · see citing works
ACh dilates pial arterioles in endothelial and neuronal NOS knockout mice by NO-dependent mechanisms
Meng, W., Ma, J., Ayata, C., Hara, H., Huang, P. L., Fishman, M. C., & Moskowitz, M. A. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.3.h1145 · Cited by 111 · see citing works
Elrod, J. W., Greer, J. J. M., Bryan, N. S., Langston, W., Szot, J. F., Gebregzlabher, H., Janssens, S. P., Feelisch, M., & Lefer, D. J. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000224324.52466.e6 · Cited by 98 · see citing works
Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases
Tsutsui, M., Shimokawa, H., Morishita, T., Nakashima, Y., & Yanagihara, N. (2006) · Journal of Pharmacological Sciences · doi:10.1254/jphs.cpj06015x · Cited by 86 · see citing works
Mouse Models of Nitric Oxide Synthase Deficiency
Huang, P. L. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v11suppl_2s120 · Cited by 79 · see citing works
Limb reduction defects in endothelial nitric oxide synthase-deficient mice
Gregg, A. R., Schauer, A., Ou, S., Liu, Z., Lee, C. G. L., & O’Brien, W. E. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.275.6.h2319 · Cited by 73 · see citing works
Nitric Oxide Inhibits α2-Adrenoceptor–Mediated Endothelium-Dependent Vasodilation
Thorin, É., Huang, P. L., Fishman, M. C., & Bevan, J. A. (1998) · Circulation Research · doi:10.1161/01.res.82.12.1323 · Cited by 72 · see citing works
Toxicology: Nitrosamines and human cancer: proof of an association?
Craddock, V. M. (1983) · Nature · doi:10.1038/306638a0 · Cited by 67 · see citing works
Compensatory mechanisms influence hemostasis in setting of eNOS deficiency
Iafrati, M. D., Vitseva, O. I., Tanrıverdi, K., Blair, P. S., Rex, S., Chakrabarti, S., Varghese, S., & Freedman, J. E. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00819.2004 · Cited by 56 · see citing works
Nitrite metabolism by skeletal muscle mitochondria in relation to haem pigments
Walters, C. L., Casselden, R. J., & Taylor, A. M. (1967) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(67)90085-0 · Cited by 52 · see citing works
Gödecke, A., & Schrader, J. (2000) · Basic Research in Cardiology · doi:10.1007/s003950070026 · Cited by 36 · see citing works
ARTICLE XI. ON THE PHYSIOLOGICAL ACTION OF POTASSIUM NITRITE
REICHERT, E. T., & MITCHELL, S. W. (1880) · The American Journal of the Medical Sciences · doi:10.1097/00000441-188007000-00011 · Cited by 27 · see citing works
[Nitrate and nitrite reductase activity of milk xanthine oxidase].
Alikulov, Z. A., Np, L., & Vl, K. (1980) · PubMed · Cited by 25 · see citing works
Disruption of the endothelial nitric oxide synthase gene: effect on vascular response to injury
Huang, P. L. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00679-1 · Cited by 23 · see citing works
Nitrite in saliva increases gastric mucosal blood flow and mucus thickness
Björne, H., Petersson, J. H., Phillipson, M., Weitzberg, E., Holm, L. P., & Lundberg, J. O. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419019 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [24]Elrod JW, Greer JJ, Bryan NS, Langston W, Szot JF, Gebregzlabher H, Janssen S, Feelisch M, Lefer DJ. Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol. 2006;26:1517–1523. doi: 10.1161/01.ATV.0000224324.52466.e6. [[DOI](https://doi.org/10.1161/01.ATV.0000224324.52466.e6)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16645153/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Arterioscler%20Thromb%20Vasc%20Biol&title=Cardiomyocyte-specific%20overexpression%20of%20NO%20synthase-3%20protects%20against%20myocardial%20ischemia-reperfusion%20injury&author=JW%20Elrod&author=JJ%20Greer&author=NS%20Bryan&author=W%20Langston&author=JF%20Szot&volume=26&publication_year=2006&pages=1517-1523&pmid=16645153&doi=10.1161/01.ATV.0000224324.52466.e6&)] · DOI
- [42]Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nature Medicine. 1995;1:804–809. doi: 10.1038/nm0895-804. [[DOI](https://doi.org/10.1038/nm0895-804)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7585184/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Nature%20Medicine&title=Enzyme-independent%20formation%20of%20nitric%20oxide%20in%20biological%20tissues&author=JL%20Zweier&author=P%20Wang&author=A%20Samouilov&author=P%20Kuppusamy&volume=1&publication_year=1995&pages=804-809&pmid=7585184&doi=10.1038/nm0895-804&)] · DOI · Paper page
- [50]Reichert ET, Mitchell SW. On the physiological action of potassium nitrite, with a note on the physiological action on man. Am J Med Sci. 1880;159:158–180. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Am%20J%20Med%20Sci&title=On%20the%20physiological%20action%20of%20potassium%20nitrite,%20with%20a%20note%20on%20the%20physiological%20action%20on%20man&author=ET%20Reichert&author=SW%20Mitchell&volume=159&publication_year=1880&pages=158-180&)]
- [60]Program NT. In: On The Toxicology and Carcinogenesis Studues of Sodium Nitrite. Services, U. S. D. o. H. a. H., ed., editor. National Institute of Health; 2001. pp. 1–276. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=On%20The%20Toxicology%20and%20Carcinogenesis%20Studues%20of%20Sodium%20Nitrite&author=NT%20Program&publication_year=2001&)]
Cited by
Sorted by citations
Food sources of nitrates and nitrites: The physiologic context for potential health benefits
Hord, N. G., Tang, Y., & Bryan, N. S. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27131 · Cited by 1,069 · see citing works
“Indeed, the Bryan laboratory has shown that nitrite can restore vascular tone after ischemia/reperfusion and substitutes for loss of eNOS-derived nitric oxide in eNOS-deficient mice (31, 32).”
BackgroundInfluentialSelf-citationMaia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401 · see citing works
Roles of dietary inorganic nitrate in cardiovascular health and disease
Lundberg, J. O., Carlström, M., Larsen, F. J., & Weitzberg, E. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq325 · Cited by 355 · see citing works
Lehnert, N., Kim, E., Dong, H. T., Harland, J. B., Hunt, A. P., Manickas, E. C., Oakley, K. M., Pham, J., Reed, G. C., & Alfaro, V. S. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00253 · Cited by 277 · see citing works
Hyde, E. R., Andrade, F., Vaksman, Z., Parthasarathy, K., Jiang, H., Parthasarathy, D. K., Torregrossa, A. C., Tribble, G., Kaplan, H. B., Petrosino, J. F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088645 · Cited by 275 · see citing works
“Numerous studies have shown that nitrite produced from bacterial nitrate reduction is an important storage pool for NO in blood and tissues when NOS-mediated NO production is insufficient [14,18,19,20,21].”
BackgroundSelf-citationSindler, A. L., Fleenor, B. S., Calvert, J. W., Marshall, K. D., Zigler, M. L., Lefer, D. J., & Seals, D. R. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00679.x · Cited by 218 · see citing works
“Sodium nitrite administration protects against ischemia ⁄ reperfusion injury (Bryan et al., 2007, 2008; Gonzalez et al., 2008) and improves vascular endothelial dysfunction in hypercholesterolemic mice (Stokes et al., 2009).”
BackgroundMethodResultInfluentialSelf-citationProtein <i>S</i> -Nitrosylation and Cardioprotection
Sun, J., & Murphy, E. (2010) · Circulation Research · doi:10.1161/circresaha.109.209452 · Cited by 205 · see citing works
Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers
Sobko, T., Marcus, C., Govoni, M., & Kamiya, S. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.007 · Cited by 185 · see citing works
“Today we are facing a paradigm shift, and the recent description of the vasoprotective, blood pressure-lowering, and antiplatelet aggregation properties of nitrite suggests that a re-examination of these health effects would be beneficial [5,43,44].”
BackgroundStokes, K. Y., Dugas, T. R., Tang, Y., Garg, H., Guidry, E., & Bryan, N. S. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01291.2008 · Cited by 171 · see citing works
“We have previously shown that nitrite supplementation in drinking water (50 mg/l sodium nitrite, 1 wk) can replete NO homeostasis and biochemistry in eNOS knockout mice (10).”
BackgroundInfluentialGilchrist, M., Winyard, P. G., & Benjamin, N. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.005 · Cited by 157 · see citing works
Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits
Machha, A., & Schechter, A. N. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0192-5 · Cited by 146 · see citing works
“In another study, the eNOSdeficient mouse has been used to investigate the effect of nitrite supplementation (50 mg/L, in drinking water) on steady-state nitrite and NO metabolite levels and on severity of myocardial IR injury [21].”
BackgroundMethodOral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure
Bryan, N. S., Tribble, G., & Angelov, N. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0725-2 · Cited by 137 · see citing works
Seals, D. R., Kaplon, R. E., Gioscia‐Ryan, R. A., & LaRocca, T. J. (2014) · Physiology · doi:10.1152/physiol.00059.2013 · Cited by 138 · see citing works
“, green leafy vegetables or beetroot) (15, 110, 218) may exert similar beneficial effects.”
Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients
Bryan, N. S., & Ivy, J. L. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.06.001 · Cited by 131 · see citing works
“drinking water consistently use 50 mg/L sodium nitrite [14,38,54,55].”
BackgroundSelf-citationThe Key Role of Nitric Oxide in Hypoxia: Hypoxic Vasodilation and Energy Supply–Demand Matching
Umbrello, M., Dyson, A., Feelisch, M., & Singer, M. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4979 · Cited by 131 · see citing works
“Orally administered NO 3 - or NO 2 - can modulate the endogenous NO system in various physiologic and patho-physiologic conditions (41, 241, 249).”
Hazim, S., Curtis, P. J., Schär, M. Y., Ostertag, L. M., Kay, C. D., Minihane, A. M., & Cassidy, A. (2016) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.125690 · Cited by 130 · see citing works
“To control for the potential confounding effect on vascular function of nitrate intake on circulating nitrite (NO2 (2)) and NO (24), participants were also instructed to avoid NO2 (2)- and nitrate (NO3 (2))-rich foods (for 24 h; a list was provided) and to consume low NO2 (2)- and NO3 (2)-containing commercially avail…”
Aragón, J. P., Condit, M. E., Bhushan, S., Predmore, B. L., Patel, S., Grinsfelder, D. B., Gundewar, S., Jha, S. K., Calvert, J. W., Barouch, L. A., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.09.033 · Cited by 127 · see citing works
Milkowski, A., Garg, H. K., Coughlin, J. R., & Bryan, N. S. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.08.004 · Cited by 123 · see citing works
“We now know that nitrite is just as efficacious when given orally at restoring NO biochemistry [88], reversing hypertension from NOS inhibition [89], protecting from myocardial ischemia–reperfusion injury [90], inhibiting microvascular inflammation, reversing endothelial dysfunction and reducing levels of C-reactive p…”
BackgroundThe Role of Nitrate in Human Health
Bryan, N. S., & van Grinsven, H. J. M. (2013) · Advances in agronomy · doi:10.1016/b978-0-12-407247-3.00003-2 · Cited by 121 · see citing works
Headaches: a Review of the Role of Dietary Factors
Zaeem, Z., Zhou, L. W., & Dilli, E. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0702-1 · Cited by 122 · see citing works
Dungel, P., Hartinger, J., Chaudary, S., Slezak, P., Hofmann, A. T., Hausner, T., Straßl, M., Wintner, E., Redl, H. R., & Mittermayr, R. (2014) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22299 · Cited by 111 · see citing works
“Under hypoxic conditions nitrite can be reduced back to NO and has been shown to mediate cytoprotection from ischemia-reperfusion injury [27].”
BackgroundSindelar, J. J., & Milkowski, A. L. (2011) · Cited by 111 · see citing works
The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications
Dal-Ros, S., & Sigrist, S. (2016) · Diseases · doi:10.3390/diseases4030024 · Cited by 112 · see citing works
“This evidence has been shown by several in vitro and in vivo animal models [324–326] and in humans [325,327,328] to increase the bioavailability of NO to reduce vascular tone, blood pressure, and micro- and macrovascular complications, and improving insulin sensitivity is certainly an attractive therapeutic target in…”
BackgroundBaliga, R. S., Milsom, A. B., Ghosh, S. M., Trinder, S. L., MacAllister, R. J., Ahluwalia, A., & Hobbs, A. J. (2012) · Circulation · doi:10.1161/circulationaha.112.100586 · Cited by 110 · see citing works
Dietary nitrite improves insulin signaling through GLUT4 translocation
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.809 · Cited by 105 · see citing works
Characterization of the rat oral microbiome and the effects of dietary nitrate
Hyde, E. R., Luk, B., Cron, S., Kusic, L., McCue, T., Bauch, T., Kaplan, H., Tribble, G., Petrosino, J. F., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.09.017 · Cited by 103 · see citing works
“To determine whether we could recapitulate the blood pressureraising effects of chlorhexidine treatment and to characterize the oral microbiomes of rats treated with chlorhexidine, we treated NaNO3-supplemented rats twice a day with chlorhexidine following a method previously utilized by our group [15].”
BackgroundMethodZand, J., Lanza, F., Garg, H. K., & Bryan, N. S. (2011) · Nutrition Research · doi:10.1016/j.nutres.2011.03.008 · Cited by 101 · see citing works
“Dietary supplementation of nitrite and nitrate in mice has shown to reverse endothelial dysfunction, suppress microvascular inflammation, reduce levels of C-reactive protein in mice subjected to a high-cholesterol diet [23], and protect from ischemia reperfusion injury [24,42,43].”
BackgroundSelf-citationNitric oxide and hydrogen sulfide: the gasotransmitter paradigm of the vascular system
Cirino, G., Vellecco, V., & Bucci, M. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13815 · Cited by 98 · see citing works
“Dysregulation of this system is involved in several diseases such as heart failure, stroke, preeclampsia and pulmonary hypertension (Moya et al., 2002; Bryan et al., 2008; Kunieda et al., 2008; Foster et al., 2009; Gonzalez et al., 2009; Que et al., 2009).”
BackgroundHECKE, T. V., Camp, J. V., & SMET, S. D. (2017) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12248 · Cited by 98 · see citing works
S-Nitrosylation signaling regulates cellular protein interactions
Marozkina, N. V., & Gaston, B. M. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.06.017 · Cited by 98 · see citing works
Jädert, C., Petersson, J., Massena, S., Ahl, D., Grapensparr, L., Holm, L., Lundberg, J. O., & Phillipson, M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.018 · Cited by 97 · see citing works
Dietary Nitrates, Nitrites, and Cardiovascular Disease
Hord, N. G. (2011) · Current Atherosclerosis Reports · doi:10.1007/s11883-011-0209-9 · Cited by 97 · see citing works
Zhu, S.-G., Kukreja, R. C., Das, A., Chen, Q., Lesnefsky, E. J., & Xi, L. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.01.024 · Cited by 96 · see citing works
The nitrate‐nitrite‐nitric oxide pathway: Its role in human exercise physiology
Bailey, S. J., Vanhatalo, A., Winyard, P. G., & JONES, A. M. (2011) · European Journal of Sport Science · doi:10.1080/17461391.2011.635705 · Cited by 96 · see citing works
“This pathway of NO synthesis complements the more recognised NOS-NO pathway to preserve NO production when NOS activity is compromised (Bryan et al., 2008; Calström et al., 2010).”
BackgroundInfluentialNO-Rich Diet for Lifestyle-Related Diseases
Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
Kina-Tanada, M., Sakanashi, M., Tanimoto, A., Kaname, T., Matsuzaki, T., Noguchi, K., Uchida, T., Nakasone, J., Kozuka, C., Ishida, M., et al. (2017) · Diabetologia · doi:10.1007/s00125-017-4259-6 · Cited by 95 · see citing works
Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function
Shiva, S., & Gladwin, M. T. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0009-3 · Cited by 91 · see citing works
“Nitrite has now been shown by a number of investigators to be cytoprotective in animal models of I/R in the heart [ 8 , 21, 52, 57], liver [21, 52, 53], brain [33] and kidney [55].”
BackgroundMethodEvolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy
Kato, G. J. (2008) · JAMA · doi:10.1001/jama.2008.598 · Cited by 85 · see citing works
Caplin, B., Wang, Z., Slaviero, A., Tomlinson, J. A. P., Dowsett, L., Delahaye, M., Salama, A. D., Wheeler, D. C., & LEIPER, J. M. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.254078 · Cited by 83 · see citing works
Myocardial protection by nitrite
Calvert, J. W., & Lefer, D. J. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp079 · Cited by 82 · see citing works
“Recent data have also shown that dysfunction of either source can result in an exacerbation of injury following myocardial ischaemia.(82,83) For example, mice deficient in eNOS (eNOS) exhibit reduced steady-state levels of both plasma and cardiac nitrite levels when compared with wildtype mice,(80,83) whereas, transge…”
BackgroundResultEffect of Blood Nitrite and Nitrate Levels on Murine Platelet Function
Park, J. W., Piknova, B., Huang, P. L., Noguchi, C. T., & Schechter, A. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055699 · Cited by 82 · see citing works
“The roles of nitrite and nitrate as exogenous NO sources have recently obtained increasing attention with respect to their potential beneficial effects in cardiovascular diseases [29,30,31].”
BackgroundDeVan, A. E., Johnson, L. C., Brooks, F. A., Evans, T. D., Justice, J. N., Cruickshank-Quinn, C. I., Reisdorph, N. A., Bryan, N. S., McQueen, M. B., Santos‐Parker, J. R., et al. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00879.2015 · Cited by 82 · see citing works
“reduced under physiological conditions by a one-step reaction to NO in a manner independent of the enzyme endothelial nitric oxide synthase (eNOS) (5).”
BackgroundEnhanced XOR activity in eNOS-deficient mice
Peleli, M., Zollbrecht, C., Montenegro, M. F., Hezel, M. P., Zhong, J., Persson, E., Holmdahl, R., Weitzberg, E., Lundberg, J. O., & Carlström, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.09.004 · Cited by 76 · see citing works
Beneficial effects of inorganic nitrate/nitrite in type 2 diabetes and its complications
Bahadoran, Z., Ghasemi, A., Mirmiran, P., Azizi, F., & Hadaegh, F. (2015) · Nutrition & Metabolism · doi:10.1186/s12986-015-0013-6 · Cited by 82 · see citing works
“Supplementation with sodium nitrate in eNOS-deficient mice with features of metabolic syndrome reduced blood pressure [41]; a similar effect was also observed following treatment with inorganic nitrate in hypertensive and eNOS deficient rat, against hypertension and myocardial ischemia-reperfusion injury [20, 55]; the…”
BackgroundIngram, T. E., Fraser, A. G., Bleasdale, R. A., Ellins, E. A., Margulescu, A. D., Halcox, J. P., & James, P. E. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.03.050 · Cited by 69 · see citing works
Nitrite and nitrate: cardiovascular risk–benefit and metabolic effect
Tang, Y., Jiang, H., & Bryan, N. S. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328341942c · Cited by 69 · see citing works
Self-citationInorganic nitrite supplementation for healthy arterial aging
Sindler, A. L., DeVan, A. E., Fleenor, B. S., & Seals, D. R. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01100.2013 · Cited by 68 · see citing works
“Much of the initial work on the cardiovascular effects of nitrite shows that pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
BackgroundEffects of Endogenous Nitric Oxide and of DETA NONOate in Arteriogenesis
Troidl, K., Tribulova, S., Cai, W.-J., Rüding, I., Apfelbeck, H., Schierling, W., Troidl, C., Schmitz‐Rixen, T., & Schaper, W. K. A. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181c9556f · Cited by 66 · see citing works
Rassaf, T., Ferdinandy, P., & Schulz, R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12291 · Cited by 62 · see citing works
“for 1 week restored NO homeostasis also in eNOS knockout mice, normally having reduced NO and NO metabolites, and protected against ischaemia/reperfusion injury (Bryan et al., 2008).”
BackgroundEffect of dietary nitrate levels on nitrate fluxes in rat skeletal muscle and liver
Gilliard, C. N., Lam, J. K., Cassel, K. S., Park, J. W., Schechter, A. N., & Piknova, B. (2018) · Nitric Oxide · doi:10.1016/j.niox.2018.01.010 · Cited by 63 · see citing works
The role of vascular myoglobin in nitrite-mediated blood vessel relaxation
Ormerod, J. O. M., Ashrafian, H., Maher, A. R., Arif, S., Steeples, V., Born, G. V. R., Egginton, S., Feelisch, M., Watkins, H., & Frenneaux, M. P. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq299 · Cited by 61 · see citing works
“that under certain circumstances, nitrite may be reduced back to nitric oxide to elicit vasorelaxation(1,2) and confer protection against ischaemia-reperfusion injury.(3) –6 While there is an increasing appreci-”
BackgroundVitturi, D. A., & Patel, R. P. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.037 · Cited by 59 · see citing works
“The observation that in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO fo…”
BackgroundGlobin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells
Corti, P., Xue, J., Tejero, J., Wajih, N., Sun, M., Stolz, D. B., Tsang, M., Kim‐Shapiro, D. B., & Gladwin, M. T. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522670113 · Cited by 55 · see citing works
“The role of nitrite as an exogenous source of NO has gathered increasing attention as it can increase NO bioavailability under physiological hypoxemic conditions and provide beneficial effects in the treatment of cardiovascular diseases (33, 34).”
BackgroundMaia, L. B., & Moura, J. J. G. (2018) · Redox Biology · doi:10.1016/j.redox.2018.08.020 · Cited by 56 · see citing works
Perlman, D. H., Bauer, S. M., Ashrafian, H., Bryan, N. S., Garcia-Saura, M. F., Lim, C. C., Fernandez, B. O., Infusini, G., McComb, M. E., Costello, C. E., et al. (2009) · Circulation Research · doi:10.1161/circresaha.108.187005 · Cited by 56 · see citing works
Antioxidant and antihypertensive responses to oral nitrite involves activation of the Nrf2 pathway
Amaral, J. H., Rizzi, É., Alves-Lopes, R., Pinheiro, L. C., Tostes, R. C., & Tanus-Santos, J. E. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.06.028 · Cited by 54 · see citing works
Alexander, J. T., El-Ali, A. M., Newman, J. L., Karatela, S., Predmore, B. L., Lefer, D. J., Sutliff, R. L., & Roback, J. D. (2013) · Transfusion · doi:10.1111/trf.12111 · Cited by 48 · see citing works
“At the time of measurement, plasma samples were thawed on ice and nitrite and nitrate concentrations were quantified by ion chromatography using an analyzer (ENO20, Eicom USA, San Diego, CA) as previously described.(36)”
MethodZhao, J., Wang, J., Yang, Y., & Lu, Y. (2015) · Journal of Chromatographic Science · doi:10.1093/chromsci/bmu212 · Cited by 46 · see citing works
“NO is readily scavenged by oxyhemoglobin in blood, forming nitrate (7, 8).”
BackgroundNitrite and myocardial ischaemia reperfusion injury. Where are we now?
Griffiths, K., Lee, J. J., Frenneaux, M. P., Feelisch, M., & Madhani, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107819 · Cited by 46 · see citing works
The oral microbiome, nitric oxide and exercise performance
Bryan, N. S., Burleigh, M. C., & Easton, C. (2022) · Nitric Oxide · doi:10.1016/j.niox.2022.05.004 · Cited by 46 · see citing works
Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients
Neuman, R., Hayek, S. S., Rahman, A. M., Poole, J. C., Menon, V., Sher, S., Newman, J. L., Karatela, S., Polhemus, D. J., Lefer, D. J., et al. (2014) · Transfusion · doi:10.1111/trf.12919 · Cited by 41 · see citing works
Singh, M., Arya, A., Kumar, R., Bhargava, K., & Sethy, N. K. (2012) · Nitric Oxide · doi:10.1016/j.niox.2011.12.002 · Cited by 38 · see citing works
Bailey, S. J., Blackwell, J. R., Wylie, L. J., Holland, T., Winyard, P. G., & JONES, A. M. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.10.002 · Cited by 38 · see citing works
“13 suggested that cigarette smoking impairs NO generation through eNOS, by lowering eNOS expression [62] and/or promoting eNOS uncoupling [63], and that the chemical reduction of NO2 can compensate for the perturbed cardiovascular function associated with NOS dysfunction [64-66].”
BackgroundSohn, H., Chang, Y. H., Yune, J. H., Jeong, C. H., Shin, D., Kwon, H.-C., Kim, D. H., Hong, S. W., Hwang, H., Jeong, J. Y., et al. (2020) · Foods · doi:10.3390/foods9121777 · Cited by 35 · see citing works
Bhushan, S., Kondo, K., Predmore, B. L., Zlatopolsky, M., King, A. L., Pearce, C., Huang, H., Tao, Y., Condit, M. E., & Lefer, D. J. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.251769 · Cited by 35 · see citing works
“Nitrite and nitrate concentrations were quantified by ion chromatography (ENO20 Analyzer; Eicom, San Diego, CA), and total nitrosothiols (RXNO) were quantified using a chemiluminescent detector (Eco Physics, Ann Arbor, MI) as previously described.(15,28)”
MethodPotential benefits of dietary nitrate ingestion in healthy and clinical populations: A brief review
McDonagh, S. T. J., Wylie, L. J., Thompson, C., Vanhatalo, A., & JONES, A. M. (2018) · European Journal of Sport Science · doi:10.1080/17461391.2018.1445298 · Cited by 34 · see citing works
Cardioprotective actions of nitrite therapy and dietary considerations
Nathan, S. B. (2009) · Frontiers in bioscience · doi:10.2741/3568 · Cited by 34 · see citing works
Sanches-Lopes, J. M., Ferreira, G. C., Pinheiro, L. C., Kemp, R., & Tanus-Santos, J. E. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113940 · Cited by 32 · see citing works
Tropea, T., Renshall, L. J., Nihlén, C., Weitzberg, E., Lundberg, J. O., David, A. L., Tsatsaris, V., Stuckey, D. J., Wareing, M., Greenwood, S. L., et al. (2020) · The Journal of Physiology · doi:10.1113/jp279655 · Cited by 32 · see citing works
“In addition to NOS-derived NO, there is now abundant evidence that NO can be generated by an alternative NOS-independent pathway: the reduction of exogenous or dietary nitrate to nitrite, and subsequently NO (Lundberg & Govoni, 2004; Bryan et al. 2008; Lundberg & Weitzberg, 2010).”
BackgroundNitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications
Tang, Y., Garg, H. K., Geng, Y., & Bryan, N. S. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.06.024 · Cited by 32 · see citing works
Justice, J. N., Gioscia‐Ryan, R. A., Johnson, L. C., Battson, M. L., de Picciotto, N., Beck, H. J., Jiang, H., Sindler, A. L., Bryan, N. S., Enoka, R. M., et al. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00608.2014 · Cited by 31 · see citing works
Inhibitory effect of nitrite on coagulation processes demonstrated by thrombelastography
Park, J., Piknova, B., Nghiem, K., Lozier, J. N., & Schechter, A. N. (2014) · Nitric Oxide · doi:10.1016/j.niox.2014.05.006 · Cited by 29 · see citing works
Cai, Y. G., Zhang, B., Shalamu, A., Gao, T., & Ge, J. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-2583 · Cited by 28 · see citing works
“Previous studies have shown that the lack of NO synthase can lead to spontaneous myocardial infarction and the aggravation of myocardial ischemia-reperfusion injury (35-37).”
BackgroundEmerging role of nitrite in myocardial protection
Lefer, D. J. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1804-y · Cited by 27 · see citing works
“This is supported by the findings of a follow-up study by this same group which evaluated steady-state nitrite and NO metabolite levels in the plasma and hearts of eNOS -/- supplemented with nitrite (50 mg/L) in their drinking water for 7 days (Bryan et al., 2008).”
BackgroundResultQuantitative aspects of nitric oxide production from nitrate and nitrite
Ghasemi, A. (2022) · EXCLI journal · doi:10.17179/excli2022-4727 · Cited by 27 · see citing works
de Prati, A. C., Podesser, B. K., Faggian, G. G., Scarabelli, T. M., Mazzucco, A., Darra, E., Rungatscher, A., Hallström, S., & Suzuki, H. (2010) · Thrombosis and Haemostasis · doi:10.1160/th09-08-0554 · Cited by 26 · see citing works
Dietary nitrate biochemistry and physiology. An update on clinical benefits and mechanisms of action
Bryan, N. S., Ahmed, S., Lefer, D. J., Hord, N. G., & Schwarz, E. R. (2023) · Nitric Oxide · doi:10.1016/j.niox.2023.01.003 · Cited by 26 · see citing works
Concentration- and stage-specific effects of nitrite on colon cancer cell lines
Jiang, H., Tang, Y., Garg, H. K., Parthasarathy, D. K., Torregrossa, A. C., Hord, N. G., & Bryan, N. S. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.010 · Cited by 25 · see citing works
Jones, J. A., Ninnis, J. R., Hopper, A. O., Ibrahim, Y., Merritt, T. A., Wan, K., Power, G. G., & Blood, A. B. (2013) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607113496118 · Cited by 24 · see citing works
“65 mg•kg (1)•day of nitrate, based on an average of 7 studies summarized by Pennington.(39) Thus, on a per kg body weight basis, neonatal intake of nitrite and nitrate are only ~0.”
InfluentialOuyang, M., Ouyang, X., Peng, Z., Liu, M., Xu, G., Zou, Z., Zhang, M., & Shang, Q. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01457-y · Cited by 23 · see citing works
Nicholson, C. K., Lambert, J. P., Chow, C.-W., Lefer, D. J., & Calvert, J. W. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.08.002 · Cited by 22 · see citing works
“NO generation was then measured in the presence and absence of nitrite (200 μM) as described previously [20].”
The Nitrate–Nitrite–Nitric Oxide Pathway in Mammals
Lundberg, J. O., Weitzberg, E., Shiva, S., & Gladwin, M. T. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-616-0_3 · Cited by 26 · see citing works
Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines
Jiang, H., Torregrossa, A. C., Parthasarathy, D. K., & Bryan, N. S. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/873210 · Cited by 21 · see citing works
“The described benefits of these ancient medications may be attributed to their inherent nitrate/nitrite content combined with their robust nitrate/nitrite reductase activity to generate NO independent of the L-arginine-NO pathway [14, 26, 32, 50].”
BackgroundPortella, R. D. L., Bickta, J., & Shiva, S. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6260 · Cited by 21 · see citing works
“Modulation of both dietary and NOS-derived nitrite levels has been shown to regulate the ischemic response, demonstrating that endogenous nitrite is a potential physiological modulator of ischemic tolerance (21, 85, 181, 196, 227).”
InfluentialGumanova, N. G. (2021) · Russian Journal of Preventive Medicine · doi:10.17116/profmed202124091102 · Cited by 22 · see citing works
Nitrite attenuated peroxynitrite and hypochlorite generation in activated neutrophils
Ren, X., Ding, Y., & Lu, N. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.02.020 · Cited by 21 · see citing works
Polhemus, D. J., Bradley, J., Islam, K. N., Brewster, L. P., Calvert, J. W., Tao, Y., Chang, C. C., Pipinos, I. I., Goodchild, T. T., & Lefer, D. J. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00115.2015 · Cited by 19 · see citing works
“Nitrite has been shown to be cytoprotective in numerous animal models of ischemic injury, including myocardial ischemia-reperfusion injury (19, 31, 38), heart failure (6), cerebral vasospasm (36), and hindlimb ischemia (6, 10, 19, 26).”
BackgroundSui, Y., Tian, R., & Lu, N. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.05.002 · Cited by 20 · see citing works
Pinheiro, L. C., Ferreira, G. C., de Angelis, C. D., Toledo, J. C., & Tanus-Santos, J. E. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.03.006 · Cited by 19 · see citing works
Current clinical framework on nitric oxide role in periodontal disease and blood pressure
Lima, L. L. L., Gaspar, S. R., Rocha, B. S., Alves, R. C., & Almeida, M. G. (2024) · Clinical Oral Investigations · doi:10.1007/s00784-024-05913-x · Cited by 21 · see citing works
“So, the bioactivation of nitrite into NO is now recognized as having an important role in hypoxic vasoregulation [1, 6–8], placing nitrite at the forefront of ‘NO biology’.”
BackgroundInfluence of Dietary Nitrate Supplementation on Exercise Tolerance and Performance
JONES, A. M., Vanhatalo, A., & Bailey, S. J. (2013) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000345815 · Cited by 19 · see citing works
Excessive Nitrite Affects Zebrafish Valvulogenesis through Yielding Too Much NO Signaling
Li, J., Jia, W., & Zhao, Q. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092728 · Cited by 18 · see citing works
“reduction of salivary nitrate [1,32,33].”
Park, J. W., Piknova, B., Walter, P. J., Cai, H., Upanan, S., Thomas, S. M., Tunau-Spencer, K. J., & Schechter, A. N. (2023) · Scientific Reports · doi:10.1038/s41598-023-28190-2 · Cited by 18 · see citing works
Yang, J., Sundqvist, M. L., Zheng, X., Jiao, T., Collado, A., Tratsiakovich, Y., Mahdi, A., Tengbom, J., Mergia, E., Catrina, S., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167693 · Cited by 17 · see citing works
Mechanism of nitrite-dependent NO synthesis by human sulfite oxidase
Bender, D. A., Kaczmarek, A. T., Niks, D., Hille, R., & Schwarz, G. (2019) · Biochemical Journal · doi:10.1042/bcj20190143 · Cited by 17 · see citing works
Dietary sources of nitrite as a modulator of ischemia/reperfusion injury
Garg, H. K., & Bryan, N. S. (2009) · Kidney International · doi:10.1038/ki.2009.13 · Cited by 17 · see citing works
Bahadoran, Z., Mirmiran, P., Jeddi, S., Carlström, M., Azizi, F., & Ghasemi, A. (2019) · Free Radical Research · doi:10.1080/10715762.2019.1587168 · Cited by 17 · see citing works
“Recent investigations show that dietary inorganic NO3 and NO2 could act as substrates or backup system for endogenous generation of NO [8,25].”
BackgroundQuantitative aspects of nitric oxide production in the heart
Ghasemi, A., & Jeddi, S. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07889-x · Cited by 16 · see citing works
Naturally cured meats: Quality, safety, and chemistry
Sullivan, G. A. (2011) · doi:10.31274/etd-180810-2479 · Cited by 16 · see citing works
Gumanova, N. G. (2021) · Russian Journal of Preventive Medicine · doi:10.17116/profmed202124101119 · Cited by 14 · see citing works
- Authors
- Bryan, N. S., Calvert, J. W., Gundewar, S., & Lefer, D. J.
- Affiliations
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Lefer, David J.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 45
- Issue
- 4
- Pages
- 468-474
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2662396
- OpenAlex
- W2074088550
- Cited by
- 161
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 15 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 6
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- National Heart, Lung, and Blood Institute (R01HL093579, 2R01 HL-6049, R01HL060849)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK077380)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- dietary nitrite, nitric oxide homeostasis, endothelial nitric oxide synthase, nitrate, myocardial ischemia-reperfusion injury, cardioprotection, blood pressure, cardiovascular health, nitrite supplementation
- MeSH terms
- Animals, Diet, Homeostasis, Myocardium, Nitric Oxide, Nitrite Reductases, Nitrites, Mice, Knockout, Mice, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
