{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:58:39Z","timestamp":1783702719074,"version":"3.55.0"},"reference-count":113,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM151226"],"award-info":[{"award-number":["R35GM151226"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM151096"],"award-info":[{"award-number":["R35GM151096"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["2217757"],"award-info":[{"award-number":["2217757"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R35GM151226"],"award-info":[{"award-number":["R35GM151226"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R35GM151096"],"award-info":[{"award-number":["R35GM151096"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2217757"],"award-info":[{"award-number":["2217757"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cardiovascular diseases (CVDs), which include multiple disorders of the heart and blood vessels, are the leading causes of death. Nitric oxide (NO) is a vasodilator that regulates vascular tension. Endogenous NO is produced via the L-arginine\u2013nitric oxide synthase (NOS) pathway. In conditions of cardiovascular dysfunction, NOS activity is impaired, leading to NO deficiency. In turn, the reduction in NO bioactivity exacerbates the pathogenesis of CVDs. Exogenous intake of inorganic nitrate supplements endogenous production via the nitrate\u2013nitrite\u2013NO pathway to maintain the NO supply. Salivary glands play an essential role in the conversion of nitrate to NO, with approximately 25% of circulating nitrate being absorbed and secreted into saliva. As a result, salivary nitrate concentrations can exceed that in the blood by more than tenfold. This recycled nitrate in saliva serves as a reservoir for NO and performs NO-like functions when endogenous NO production is insufficient. In this review, we summarize the emerging benefits of dietary nitrate in CVDs, with a particular focus on salivary-gland-mediated nitrate recirculation in maintaining NO bioavailability and cardiovascular homeostasis. Salivary-gland-mediated nitrate recirculation provides a novel perspective for potential intervention of CVDs.<\/jats:p>","DOI":"10.3390\/biom15030439","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:48:37Z","timestamp":1742370517000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases"],"prefix":"10.3390","volume":"15","author":[{"given":"Baoxing","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyun","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Biology, Rutgers University, Camden, NJ 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-1219","authenticated-orcid":false,"given":"Huiliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2048004020949326","DOI":"10.1177\/2048004020949326","article-title":"Primary Prevention of Cardiovascular Disease: Updated Review of Contemporary Guidance and Literature","volume":"9","author":"Stewart","year":"2020","journal-title":"JRSM Cardiovasc. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107279","DOI":"10.1016\/j.phrs.2024.107279","article-title":"The Function and Therapeutic Potential of Transfer RNA-Derived Small RNAs in Cardiovascular Diseases: A Review","volume":"206","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bryan, N.S. (2022). Nitric Oxide Deficiency Is a Primary Driver of Hypertension. Biochem. Pharmacol., 206.","DOI":"10.1016\/j.bcp.2022.115325"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1172\/JCI114904","article-title":"Role of Endothelium-Derived Nitric Oxide in the Bleeding Tendency of Uremia","volume":"86","author":"Remuzzi","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1016\/j.cell.2022.06.010","article-title":"Nitric Oxide Signaling in Health and Disease","volume":"185","author":"Lundberg","year":"2022","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Daiber, A., Xia, N., Steven, S., Oelze, M., Hanf, A., Kr\u00f6ller-Sch\u00f6n, S., M\u00fcnzel, T., and Li, H. (2019). New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function\/Dysfunction in Cardiovascular Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010187"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kr\u00f3l, M., and Kepinska, M. (2020). Human Nitric Oxide Synthase-Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010056"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.niox.2018.12.007","article-title":"Regulation of Endothelial Barrier Integrity by Redox-Dependent Nitric Oxide Signaling: Implication in Traumatic and Inflammatory Brain Injuries","volume":"83","author":"Choi","year":"2019","journal-title":"Nitric Oxide"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1124\/pharmrev.124.001060","article-title":"Nitric Oxide Signaling and Regulation in the Cardiovascular System: Recent Advances","volume":"76","author":"Weitzberg","year":"2024","journal-title":"Pharmacol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nrcardio.2017.224","article-title":"Nitric Oxide Signalling in Cardiovascular Health and Disease","volume":"15","author":"Farah","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s40001-023-01413-y","article-title":"From Nitrate to NO: Potential Effects of Nitrate-Reducing Bacteria on Systemic Health and Disease","volume":"28","author":"Liu","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_12","first-page":"e20485","article-title":"The Effects of L-Arginine in Hypertensive Patients: A Literature Review","volume":"13","author":"Abukhodair","year":"2021","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1161\/01.RES.0000088351.58510.21","article-title":"Nitric Oxide and Cardiac Function: Ten Years after, and Continuing","volume":"93","author":"Massion","year":"2003","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.pharmthera.2004.11.003","article-title":"Cardiac Nitric Oxide: Emerging Role for nNOS in Regulating Physiological Function","volume":"106","author":"Danson","year":"2005","journal-title":"Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.lfs.2007.07.019","article-title":"Nitric Oxide and Cardiac Function","volume":"81","author":"Rastaldo","year":"2007","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/cvr\/cvq214","article-title":"Cardiac Electrophysiological Effects of Nitric Oxide","volume":"87","author":"Tamargo","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrd2466","article-title":"The Nitrate-Nitrite-Nitric Oxide Pathway in Physiology and Therapeutics","volume":"7","author":"Lundberg","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.niox.2006.01.013","article-title":"Cardioprotective Effects of Vegetables: Is Nitrate the Answer?","volume":"15","author":"Lundberg","year":"2006","journal-title":"Nitric Oxide"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mam.2017.08.001","article-title":"Vegetable-Derived Bioactive Nitrate and Cardiovascular Health","volume":"61","author":"Bondonno","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0015-6264(76)80005-3","article-title":"Influence of Dietary Nitrate on Nitrite Content of Human Saliva: Possible Relevance to in Vivo Formation of N-Nitroso Compounds","volume":"14","author":"Spiegelhalder","year":"1976","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1249\/MSS.0000000000002470","article-title":"Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance","volume":"53","author":"Jones","year":"2021","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rocha, B.S. (2021). The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-Clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly. Front. Aging, 2.","DOI":"10.3389\/fragi.2021.778467"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1126\/science.1136674","article-title":"Transformation of the Nitrogen Cycle: Recent Trends, Questions, and Potential Solutions","volume":"320","author":"Galloway","year":"2008","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.niox.2011.03.307","article-title":"Nitric Oxide and Quality and Safety of Muscle Based Foods","volume":"24","author":"Skibsted","year":"2011","journal-title":"Nitric Oxide"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/317675b0","article-title":"Nitrate and Gastric Cancer Risks","volume":"317","author":"Tannenbaum","year":"1985","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmet.2018.06.007","article-title":"Metabolic Effects of Dietary Nitrate in Health and Disease","volume":"28","author":"Lundberg","year":"2018","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tan, L., Stagg, L., Hanlon, E., Li, T., Fairley, A.M., Siervo, M., Matu, J., Griffiths, A., and Shannon, O.M. (2024). Associations between Vegetable Nitrate Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review. Nutrients, 16.","DOI":"10.3390\/nu16101511"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1089\/bfm.2010.0070","article-title":"Nitrate and Nitrite Content of Human, Formula, Bovine, and Soy Milks: Implications for Dietary Nitrite and Nitrate Recommendations","volume":"6","author":"Hord","year":"2011","journal-title":"Breastfeed. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3945\/ajcn.2008.27131","article-title":"Food Sources of Nitrates and Nitrites: The Physiologic Context for Potential Health Benefits","volume":"90","author":"Hord","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Olas, B. (2024). The Cardioprotective Role of Nitrate-Rich Vegetables. Foods, 13.","DOI":"10.3390\/foods13050691"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF00377461","article-title":"Metabolic Fate of Nitric Oxide","volume":"46","author":"Yoshida","year":"1980","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11095-020-02959-w","article-title":"Simultaneous Pharmacokinetic Analysis of Nitrate and Its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population","volume":"37","author":"Coggan","year":"2020","journal-title":"Pharm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/0278-6915(85)90153-X","article-title":"Excretion of Nitrates and Nitrites in Saliva and Bile in the Dog","volume":"23","author":"Fritsch","year":"1985","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cardfail.2017.12.001","article-title":"The Nitrate-Nitrite-NO Pathway as a Novel Therapeutic Target in Heart Failure with Reduced Ejection Fraction","volume":"24","author":"Chirinos","year":"2018","journal-title":"J. Card. Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/368502a0","article-title":"Stomach NO Synthesis","volume":"368","author":"Benjamin","year":"1994","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.molmed.2009.08.002","article-title":"Hemoglobin, Nitric Oxide and Molecular Mechanisms of Hypoxic Vasodilation","volume":"15","author":"Allen","year":"2009","journal-title":"Trends Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13434","DOI":"10.1073\/pnas.1116633109","article-title":"Sialin (SLC17A5) Functions as a Nitrate Transporter in the Plasma Membrane","volume":"109","author":"Qin","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.prosdent.2021.05.009","article-title":"Novel Impacts of Saliva with Regard to Oral Health","volume":"127","author":"Uchida","year":"2022","journal-title":"J. Prosthet. Dent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1177\/154405910308200205","article-title":"Destruction of Parotid Glands Affects Nitrate and Nitrite Metabolism","volume":"82","author":"Xia","year":"2003","journal-title":"J. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.freeradbiomed.2004.04.027","article-title":"Inorganic Nitrate Is a Possible Source for Systemic Generation of Nitric Oxide","volume":"37","author":"Lundberg","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/s41440-019-0260-4","article-title":"Analysis of Oral Microbiota in Patients with Obstructive Sleep Apnea-Associated Hypertension","volume":"42","author":"Ko","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.niox.2010.01.004","article-title":"Enhanced Xanthine Oxidoreductase Expression and Tissue Nitrate Reduction in Germ Free Mice","volume":"22","author":"Huang","year":"2010","journal-title":"Nitric Oxide"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1177\/00220345221080982","article-title":"The Importance of Nitrate Reduction for Oral Health","volume":"101","author":"Rosier","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hu, X., Xu, H., Bu, L., Sun, J., Deng, J., Song, K., Wang, L., and Pang, B. (2024). Exploring the Wound Healing Potential of Dietary Nitrate in Diabetic Rat Model. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1475375"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00784-024-05913-x","article-title":"Current Clinical Framework on Nitric Oxide Role in Periodontal Disease and Blood Pressure","volume":"28","author":"Lima","year":"2024","journal-title":"Clin. Oral Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ahmad, A., Dempsey, S.K., Daneva, Z., Azam, M., Li, N., Li, P.-L., and Ritter, J.K. (2018). Role of Nitric Oxide in the Cardiovascular and Renal Systems. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092605"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1152\/jappl.2001.91.3.1421","article-title":"Invited Review: cGMP-Dependent Protein Kinase Signaling Mechanisms in Smooth Muscle: From the Regulation of Tone to Gene Expression","volume":"91","author":"Lincoln","year":"2001","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fernando, V., Zheng, X., Walia, Y., Sharma, V., Letson, J., and Furuta, S. (2019). S-Nitrosylation: An Emerging Paradigm of Redox Signaling. Antioxidants, 8.","DOI":"10.3390\/antiox8090404"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1089\/ars.2007.1993","article-title":"Reactive Nitrogen Species: Molecular Mechanisms and Potential Significance in Health and Disease","volume":"11","author":"Andriantsitohaina","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1039\/D4FO03096F","article-title":"Combination of Inorganic Nitrate and Vitamin C Prevents Collagen-Induced Arthritis in Rats by Inhibiting Pyroptosis","volume":"16","author":"Zhang","year":"2025","journal-title":"Food Funct."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Ouyang, X., Peng, Y., and Peng, S. (2021). Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111917"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"176186","DOI":"10.1016\/j.ejphar.2023.176186","article-title":"Fumarate and Its Downstream Signalling Pathways in the Cardiorenal System: Recent Insights and Novel Expositions in the Etiology of Hypertension","volume":"961","author":"Edosuyi","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3945\/jn.116.229807","article-title":"Nitrate-Rich Vegetables Increase Plasma Nitrate and Nitrite Concentrations and Lower Blood Pressure in Healthy Adults","volume":"146","author":"Jonvik","year":"2016","journal-title":"J. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/HYPERTENSIONAHA.107.103523","article-title":"Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite","volume":"51","author":"Webb","year":"2008","journal-title":"Hypertension"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.freeradbiomed.2023.11.039","article-title":"Acute and Short-Term Beetroot Juice Nitrate-Rich Ingestion Enhances Cardiovascular Responses Following Aerobic Exercise in Postmenopausal Women with Arterial Hypertension: A Triple-Blinded Randomized Controlled Trial","volume":"211","author":"Benjamim","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tawa, M., Nagata, R., Sumi, Y., Nakagawa, K., Sawano, T., Ohkita, M., and Matsumura, Y. (2021). Preventive Effects of Nitrate-Rich Beetroot Juice Supplementation on Monocrotaline-Induced Pulmonary Hypertension in Rats. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249816"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bonilla Ocampo, D.A., Paipilla, A.F., Mar\u00edn, E., Vargas-Molina, S., Petro, J.L., and P\u00e9rez-Id\u00e1rraga, A. (2018). Dietary Nitrate from Beetroot Juice for Hypertension: A Systematic Review. Biomolecules, 8.","DOI":"10.3390\/biom8040134"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1056\/NEJMc062800","article-title":"Effects of Dietary Nitrate on Blood Pressure in Healthy Volunteers","volume":"355","author":"Larsen","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jand.2020.02.014","article-title":"A Nitrate-Rich Vegetable Intervention Elevates Plasma Nitrate and Nitrite Concentrations and Reduces Blood Pressure in Healthy Young Adults","volume":"120","author":"Jonvik","year":"2020","journal-title":"J. Acad. Nutr. Diet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1161\/HYPERTENSIONAHA.114.04675","article-title":"Dietary Nitrate Provides Sustained Blood Pressure Lowering in Hypertensive Patients: A Randomized, Phase 2, Double-Blind, Placebo-Controlled Study","volume":"65","author":"Kapil","year":"2015","journal-title":"Hypertension"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.freeradbiomed.2024.02.011","article-title":"Effects of Dietary Inorganic Nitrate on Blood Pressure during and Post-Exercise Recovery: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials","volume":"215","author":"Benjamim","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.freeradbiomed.2024.07.004","article-title":"Effects of Increased Nitrate Intake from Beetroot Juice on Blood Markers of Oxidative Stress and Inflammation in Older Adults with Hypertension","volume":"222","author":"Fejes","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1111\/bph.15636","article-title":"Inorganic Nitrate Attenuates Cardiac Dysfunction: Roles for Xanthine Oxidoreductase and Nitric Oxide","volume":"179","author":"Gee","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Woessner, M.N., Levinger, I., Allen, J.D., McIlvenna, L.C., and Neil, C. (2020). The Effect of Dietary Inorganic Nitrate Supplementation on Cardiac Function during Submaximal Exercise in Men with Heart Failure with Reduced Ejection Fraction (HFrEF): A Pilot Study. Nutrients, 12.","DOI":"10.3390\/nu12072132"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"844","DOI":"10.2337\/db22-0575","article-title":"Dietary Nitrate and Corresponding Gut Microbiota Prevent Cardiac Dysfunction in Obese Mice","volume":"72","author":"Petrick","year":"2023","journal-title":"Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1161\/CIRCRESAHA.114.301475","article-title":"Nitrite Therapy Improves Left Ventricular Function during Heart Failure via Restoration of Nitric Oxide-Mediated Cytoprotective Signaling","volume":"114","author":"Bhushan","year":"2014","journal-title":"Circ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Yu, L., Jin, Z., Li, M., Liu, H., Tao, J., Xu, C., Wang, L., and Zhang, Q. (2022). Protective Potential of Hydroxysafflor Yellow A in Cerebral Ischemia and Reperfusion Injury: An Overview of Evidence from Experimental Studies. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1063035"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/1074248419892603","article-title":"Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States","volume":"25","author":"Kloner","year":"2020","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/cvr\/cvq325","article-title":"Roles of Dietary Inorganic Nitrate in Cardiovascular Health and Disease","volume":"89","author":"Lundberg","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.bja.2021.06.046","article-title":"Effects of Inorganic Nitrate on Ischaemia-Reperfusion Injury after Coronary Artery Bypass Surgery: A Randomised Controlled Trial","volume":"127","author":"Eriksson","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1017\/S0007114522002434","article-title":"Dietary Nitrate and Brain Health. Too Much Ado about Nothing or a Solution for Dementia Prevention?","volume":"128","author":"Siervo","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"676","DOI":"10.2174\/1874467214666210909154609","article-title":"Nitric Oxide Modulation as a Potential Molecular Mechanism Underlying the Protective Role of NaHS in Liver Ischemia Reperfusion Injury","volume":"15","author":"Ibrahim","year":"2022","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7540","DOI":"10.1073\/pnas.0711480105","article-title":"Chronic Sodium Nitrite Therapy Augments Ischemia-Induced Angiogenesis and Arteriogenesis","volume":"105","author":"Kumar","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0008-6363(97)00138-7","article-title":"Role of Endothelin, Nitric Oxide and L-Arginine Release in Ischaemia\/Reperfusion Injury of Rat Heart","volume":"36","author":"Brunner","year":"1997","journal-title":"Cardiovasc. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.phrs.2015.12.006","article-title":"The HNO Donor Angeli\u2019s Salt Offers Potential Haemodynamic Advantages over NO or Dobutamine in Ischaemia-Reperfusion Injury in the Rat Heart Ex Vivo","volume":"104","author":"Chin","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10256","DOI":"10.1073\/pnas.0801336105","article-title":"Nitrite Reductase Activity of Myoglobin Regulates Respiration and Cellular Viability in Myocardial Ischemia-Reperfusion Injury","volume":"105","author":"Merx","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1124\/pr.120.019240","article-title":"The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway","volume":"72","author":"Kapil","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_78","first-page":"18","article-title":"Myocardial Infarct Size Is Reduced by Nitrite and Nitrate Administration: A Systematic Review and Meta-Analysis of Animal Studies","volume":"23","author":"Yassaghi","year":"2024","journal-title":"EXCLI J."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Cui, H., Feng, Y., Shu, C., Yuan, R., Bu, L., Jia, M., and Pang, B. (2020). Dietary Nitrate Protects Against Skin Flap Ischemia-Reperfusion Injury in Rats via Modulation of Antioxidative Action and Reduction of Inflammatory Responses. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01605"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1600-0773.1991.tb01209.x","article-title":"Exogenous GTP Enhances the Effects of Sodium Nitrite on Cyclic GMP Accumulation, Vascular Smooth Muscle Relaxation and Platelet Aggregation","volume":"68","author":"Laustiola","year":"1991","journal-title":"Pharmacol. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hu, X., Wang, L., Deng, J., Xu, H., Song, K., Bu, L., and Pang, B. (2023). Dietary Nitrate Accelerates the Healing of Infected Skin Wounds in Mice by Increasing Microvascular Density. Biochem. Biophys. Res. Commun., 686.","DOI":"10.1016\/j.bbrc.2023.149176"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Joris, P.J., Mensink, R.P., Adam, T.C., and Liu, T.T. (2018). Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise. Nutrients, 10.","DOI":"10.3390\/nu10050530"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jin, L., Qin, L., Xia, D., Liu, X., Fan, Z., Zhang, C., Gu, L., He, J., Ambudkar, I.S., and Deng, D. (2013). Active Secretion and Protective Effect of Salivary Nitrate against Stress in Human Volunteers and Rats. Free Radic. Biol. Med., 57.","DOI":"10.1016\/j.freeradbiomed.2012.12.015"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1097\/CM9.0000000000000943","article-title":"Protective Effect of Dietary Nitrate on Stress-Induced Gastric Mucosal Injury via Enhancing Blood Perfusion in Mongolian Gerbils","volume":"133","author":"Pang","year":"2020","journal-title":"Chin. Med. J. (Engl.)"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12986-016-0094-x","article-title":"Impact of Flavonoid-Rich Black Tea and Beetroot Juice on Postprandial Peripheral Vascular Resistance and Glucose Homeostasis in Obese, Insulin-Resistant Men: A Randomized Controlled Trial","volume":"13","author":"Fuchs","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_86","first-page":"1307","article-title":"Nitrate Administration Increases Blood Flow in Dysfunctional but Viable Myocardium, Leading to Improved Assessment of Myocardial Viability: A PET Study","volume":"47","author":"Slart","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1017\/S0954422413000188","article-title":"The Effects of Dietary Nitrate on Blood Pressure and Endothelial Function: A Review of Human Intervention Studies","volume":"26","author":"Hobbs","year":"2013","journal-title":"Nutr. Res. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ju, J., Liu, Y., Liang, H., and Yang, B. (2022). The Role of Pyroptosis in Endothelial Dysfunction Induced by Diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1093985"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.freeradbiomed.2011.09.028","article-title":"Flavonoid-Rich Apples and Nitrate-Rich Spinach Augment Nitric Oxide Status and Improve Endothelial Function in Healthy Men and Women: A Randomized Controlled Trial","volume":"52","author":"Bondonno","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"R162","DOI":"10.1152\/ajpregu.00121.2021","article-title":"Body Mass-Normalized Moderate Dose of Dietary Nitrate Intake Improves Endothelial Function and Walking Capacity in Patients with Peripheral Artery Disease","volume":"321","author":"Pekas","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111995","DOI":"10.1016\/j.nut.2023.111995","article-title":"Is Vitamin C a Booster of the Effects of Dietary Nitrate on Endothelial Function? Physiologic Rationale and Implications for Research","volume":"109","author":"Lbban","year":"2023","journal-title":"Nutrition"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.freeradbiomed.2010.12.018","article-title":"Pathogenetic Role of eNOS Uncoupling in Cardiopulmonary Disorders","volume":"50","author":"Gielis","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1160\/TH17-06-0394","article-title":"Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study","volume":"118","author":"Abdul","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"106616","DOI":"10.1016\/j.phrs.2022.106616","article-title":"Local Delivery of Nitric Oxide Prevents Endothelial Dysfunction in Periodontitis","volume":"188","author":"Fernandes","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"E217","DOI":"10.1152\/ajpendo.00610.2020","article-title":"Independent of Mitochondrial Respiratory Function, Dietary Nitrate Attenuates HFD-Induced Lipid Accumulation and Mitochondrial ROS Emission within the Liver","volume":"321","author":"DesOrmeaux","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1113\/jphysiol.2014.275263","article-title":"Dietary Nitrate Increases Arginine Availability and Protects Mitochondrial Complex I and Energetics in the Hypoxic Rat Heart","volume":"592","author":"Ashmore","year":"2014","journal-title":"J. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Petrick, H.L., Handy, R.M., Vachon, B., Frangos, S.M., Holwerda, A.M., Gijsen, A.P., Senden, J.M., van Loon, L.J.C., and Holloway, G.P. (J. Physiol., 2023). Dietary Nitrate Preserves Mitochondrial Bioenergetics and Mitochondrial Protein Synthesis Rates during Short-Term Immobilization in Mice, J. Physiol., ahead of print.","DOI":"10.1113\/JP284701"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"0300060520902605","DOI":"10.1177\/0300060520902605","article-title":"Nitrate Partially Inhibits Lipopolysaccharide-Induced Inflammation by Maintaining Mitochondrial Function","volume":"48","author":"Yang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/cvr\/cvt050","article-title":"ROS Regulation of Microdomain Ca(2+) Signalling at the Dyads","volume":"98","author":"Zhang","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10463","DOI":"10.1073\/pnas.181191198","article-title":"Nitroxyl Anion Exerts Redox-Sensitive Positive Cardiac Inotropy in Vivo by Calcitonin Gene-Related Peptide Signaling","volume":"98","author":"Paolocci","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5537","DOI":"10.1073\/pnas.0937302100","article-title":"Positive Inotropic and Lusitropic Effects of HNO\/NO- in Failing Hearts: Independence from Beta-Adrenergic Signaling","volume":"100","author":"Paolocci","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1161\/01.RES.0000253904.53601.c9","article-title":"Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca2+ Cycling","volume":"100","author":"Tocchetti","year":"2007","journal-title":"Circ. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/CIRCRESAHA.112.270827","article-title":"Nitroxyl-Mediated Disulfide Bond Formation between Cardiac Myofilament Cysteines Enhances Contractile Function","volume":"111","author":"Gao","year":"2012","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/ncb1001-867","article-title":"Endogenous Nitric Oxide Mechanisms Mediate the Stretch Dependence of Ca2+ Release in Cardiomyocytes","volume":"3","author":"Petroff","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_105","first-page":"113","article-title":"Carcinogenic Risk from Nitrite, Nitrate and N-Nitrosamines in Food","volume":"70","author":"Swann","year":"1977","journal-title":"Proc. R. Soc. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.redox.2015.05.004","article-title":"Effects of Long-Term Dietary Nitrate Supplementation in Mice","volume":"5","author":"Hezel","year":"2015","journal-title":"Redox Biol."},{"key":"ref_107","first-page":"6225","article-title":"Histological Characteristics Following a Long-Term Nitrate-Rich Diet in Miniature Pigs with Parotid Atrophy","volume":"8","author":"Xia","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.niox.2012.03.011","article-title":"Human Safety Controversies Surrounding Nitrate and Nitrite in the Diet","volume":"26","author":"Sindelar","year":"2012","journal-title":"Nitric Oxide"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.3390\/nu6115224","article-title":"Nitrate Ingestion: A Review of the Health and Physical Performance Effects","volume":"6","author":"Clements","year":"2014","journal-title":"Nutrients"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1017\/S0029665115004255","article-title":"Processed Meat: The Real Villain?","volume":"75","author":"Rohrmann","year":"2016","journal-title":"Proc. Nutr. Soc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.freeradbiomed.2020.09.018","article-title":"Dietary Nitrite Extends Lifespan and Prevents Age-Related Locomotor Decline in the Fruit Fly","volume":"160","author":"Moretti","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Carvalho, L.R.R.A., Guimar\u00e3es, D.D., Fl\u00f4r, A.F.L., Leite, E.G., Ruiz, C.R., de Andrade, J.T., Monteiro, M.M.O., Balarini, C.M., de Lucena, R.B., and Sandrim, V.C. (2021). Effects of Chronic Dietary Nitrate Supplementation on Longevity, Vascular Function and Cancer Incidence in Rats. Redox Biol., 48.","DOI":"10.1016\/j.redox.2021.102209"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/hed.26496","article-title":"Short-Term and Long-Term Unstimulated Saliva Flow Following Unilateral vs Bilateral Radiotherapy for Oropharyngeal Carcinoma","volume":"43","author":"Huang","year":"2021","journal-title":"Head Neck"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:27Z","timestamp":1760028987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":113,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["biom15030439"],"URL":"https:\/\/doi.org\/10.3390\/biom15030439","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]}}}