Inorganic nitrate and nitrite and control of blood pressure

Cardiovascular Research

Volumn 89, Issue 3, 2011, Pages 492-498

  Gilchrist, Mark ^a   Shore, Angela C ^a   Benjamin, Nigel ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

Author keywords

Blood pressure; Diet; Nitrate; Nitric Oxide; Nitrite

Indexed keywords

AMYL NITRITE; BISMUTH NITRATE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLYCERYL TRINITRATE; NITRATE; NITRIC OXIDE SYNTHASE; NITRITE; POTASSIUM NITRITE; SODIUM NITRATE; SODIUM NITRITE; UNCLASSIFIED DRUG; XANTHINE OXIDASE;

ANGINA PECTORIS; BLOOD PRESSURE REGULATION; BRAIN BLOOD FLOW; CARDIOVASCULAR FUNCTION; DIETARY INTAKE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EXCRETION; DRUG HALF LIFE; HUMAN; HYPERTENSION; KIDNEY INJURY; METHEMOGLOBINEMIA; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; SUNLIGHT; VASODILATATION; VEGETABLE;

ANIMALS; BLOOD PRESSURE; CARDIOVASCULAR SYSTEM; HUMANS; HYPERTENSION; NITRATES; NITRITES;

EID: 79551481719     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvq309     Document Type: Review

References (117)

1. Ignarro LJ, Byrns RE, Buga GM, Wood KS. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res 1987;61:866-879.
2. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-526. (Pubitemid 17085822)
3. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989;334:997-1000.
4. Ignarro L. Endothelium-derived nitric oxide: actions and properties. FASEB J 1989;3: 31-36. (Pubitemid 19042562)
5. Mitchell HH, Shonle HA, Grindley HS. The origin of nitrates in urine. J Biol Chem 1916;24:461-90.
6. Böhme A. Ü ber Nitritvergiftung nach interner Darreichung von Bismuthum subnitri-cum. Naunyn Schmiedebergs Arch Pharmaco 1907;57:441-454.
7. Doel JJ, Benjamin N, Hector MP, Rogers M, Allaker RP. Evaluation of bacterial nitrate reduction in the human oral cavity. Eur J Oral Sci 2005;113:14-19.
8. Lundberg JO, Weitzberg E, Cole JA, Benjamin N. Nitrate, bacteria and human health. Nat Rev Microbiol 2004;2:593-602. [Erratum appears in Nat Rev Microbiol 2004;2:681].
9. Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003;9:1498-1505.
10. Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE et al. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005;115:2099-2107.
11. Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH et al. Deoxymyo-globin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res 2007;100:654-661.
12. Alzawahra WF, Talukder MA, Liu X, Samouilov A, Zweier JL, Alzawahra WF et al. Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall. Am J Physiol Heart Circ Physiol 2008;295:H499-H508.
13. Vitturi DA, Teng X, Toledo JC, Matalon S, Lancaster JR Jr, Patel RP. Regulation of nitrite transport in red blood cells by hemoglobin oxygen fractional saturation. Am J Physiol Heart Circ Physiol 2009;296:H1398-H1407.
14. Zhang Z, Naughton DP, Blake DR, Benjamin N, Stevens CR, Winyard PG et al. Human xanthine oxidase converts nitrite ions into nitric oxide (NO). Biochem Soc Trans 1997;25:524S.
15. Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 2004;101:13683-13688.
16. Lu P, Liu F, Yao Z, Wang C-Y, Chen D-D, Tian Y et al. Nitrite-derived nitric oxide by xanthine oxidoreductase protects the liver against ischemia-reperfusion injury. Hepatobiliary Pancreat Dis Int 2005;4:350-355.
17. Baker JE, Su J, Fu X, Hsu A, Gross GJ, Tweddell JS et al. Nitrite confers protection against myocardial infarction: role of xanthine oxidoreductase, NADPH oxidase and K(ATP) channels. J Mol Cell Cardiol 2007;43:437-444.
18. Golwala NH, Hodenette C, Murthy SN, Nossaman BD, Kadowitz PJ. Vascular responses to nitrite are mediated by xanthine oxidoreductase and mitochondrial aldehyde dehydrogenase in the rat. Can J Physiol Pharmacol 2009;87:1095-1101.
19. Gautier C, van Faassen E, Mikula I, Martasek P, Slama-Schwok A. Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia. Biochem Biophys Res Commun 2006;341:816-821.
20. Webb AJ, Milsom AB, Rathod KS, Chu WL, Qureshi S, Lovell MJ et al. Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase. Circ Res 2008;103:957-964.
21. Maher AR, Milsom AB, Gunaruwan P, Abozguia K, Ahmed I, Weaver RA et al. Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. Circulation 2008;117:670-677.
22. Benjamin N, O'Driscoll F, Dougall H, Duncan C, Smith L, Golden M et al. Stomach NO synthesis. Nature 1994;368:502.
23. Duncan C, Dougall H, Johnston P, Green S, Brogan R, Leifert C et al. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med 1995;1:546-551.
24. McKnight GM, Smith LM, Drummond RS, Duncan CW, Golden M, Benjamin N. Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans. Gut 1997;40:211-214.
25. Lundberg JO, Weitzberg E, Lundberg JM, Alving K. Intragastric nitric oxide production in humans: measurements in expelled air. Gut 1994;35:1543-1546.
26. Oplander C, Volkmar CM, Paunel-Gorgulu A, van Faassen EE, Heiss C, Kelm M et al. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates. Circ Res 2009;105: 1031-1040.
27. Bonnell A. Nitrate concentrations in vegetables. Epidemiological studies in humans. In: Proceedings of the International Workshop on Health Aspects of Nitrate and its Metabolites (Particularly Nitrite). Reports of the Scientific Committee for Food. Strasbourg: European Commission; 1995.
28. ECETOC. Nitrate and Drinking Water. Brussels: European Chemical Industry Ecology and Toxicolgy Centre; 1988.
29. Florin TH, Neale G, Cummings JH. The effect of dietary nitrate on nitrate and nitrite excretion in man. Br J Nutr 1990;64:387-397.
30. van Velzen AG, Sips AJAM, Schothorst RC, Lambers AC, Meulenbelt J. The oral bioavailability of nitrate from nitrate-rich vegetables in humans. Toxicol Lett 2008; 181:177-181.
31. Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SR. Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid. Cancer Res 1983;43:1921-1925.
32. Godfrey M, Majid DS. Renal handling of circulating nitrates in anesthetized dogs. Am J Physiol 1998;275:F68-F73.
33. Forte P, Copland M, Smith LM, Milne E, Sutherland J, Benjamin N. Basal nitric oxide synthesis in essential hypertension. Lancet 1997;349:837-842.
34. Forte P, Kneale BJ, Milne E, Chowienczyk PJ, Johnston A, Benjamin N et al. Evidence for a difference in nitric oxide biosynthesis between healthy women and men. Hypertension 1998;32:730-734.
35. Lundberg JO, Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 2004;37:395-400.
36. Wallace JL, Miller MJ. Nitric oxide in mucosal defense: a little goes a long way. Gastro-enterology 2000;119:512-520.
37. Bjorne HH, Petersson J, Phillipson M, Weitzberg E, Holm L, Lundberg JO. Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. [erratum appears in J Clin Invest 2004 Feb;113:490]. J Clin Invest 2004;113:106-114.
38. Petersson J, Phillipson M, Jansson EA, Patzak A, Lundberg JO, Holm L. Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol 2007;292:G718-G724.
39. Dykhuizen RS, Frazer R, Duncan C, Smith CC, Golden M, Benjamin N et al. Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. Antimicrob Agents Chemother 1996;40:1422-1425.
40. Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 2008;51:784-790.
41. Bernheim F, Dixon M. The reduction of nitrates in animal tissues. Biochem J 1928;22: 125-134.
42. Jansson EA, Huang L, Malkey R, Govoni M, Nihlen C, Olsson A et al. A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nat Chem Biol 2008;4:411-417.
43. Ishibashi T, Nishizawa N, Nomura M, Liu S, Yang M, Miwa T et al. Arteriovenous differences in NO2- kinetics in anesthetized rabbits. Biol Pharm Bull 2009;32: 399-404.
44. Kelm M. Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1999;1411: 273-289.
45. Kim-Shapiro DB, Gladwin MT, Patel RP, Hogg N. The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation. J Inorg Biochem 2005;99:237-246.
46. Chen K, Piknova B, Pittman RN, Schechter AN, Popel AS. Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes. Nitric Oxide 2008;18: 47-60.
47. Kim Y-M, Lancaster JR Jr. Tetrahydrobiopterin-dependent nitrite oxidation to nitrate in isolated rat hepatocytes. FEBS Lett 1993;332:255-259.
48. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 2005;1:290-297.
49. Rodriguez J, Maloney RE, Rassaf T, Bryan NS, Feelisch M. Chemical nature of nitric oxide storage forms in rat vascular tissue. Proc Natl Acad Sci USA 2003;100:336-341.
50. Tripatara P, Patel NSA, Webb A, Rathod K, Lecomte FMJ, Mazzon E et al. Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. J Am Soc Nephrol 2007;18:570-580.
51. Brunton T. On the use of nitrite of amyl in angina pectoris. Lancet 1867;2:97-98.
52. Reichert ET. On the physiological action of potassium nitrite. Am J Med Sci 1880;80: 158-180.
53. Collier W. A case of angina pectoris treated with nitrite of sodium: remarks. Lancet 1883;122:901.
54. Wallace GB, Ringer AI. The lowering of blood pressure by the nitrite group. JAMA 1909;LIII:1629-1630.
55. Stieglitz EJ. Bismuth subnitrate in the therapy of hypertension. J Pharmacol Exp Ther 1927;32:23-35.
56. Stieglitz EJ. Bismuth subnitrate in the treatment of arterial hypertension. JAMA 1930; 95:842-846.
57. Nitrites, nitrosamines, and cancer. Lancet 1968;291:1071-1072.
58. Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M et al. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 2001;98:12814-12819.
59. Casey DB, Badejo AM Jr, Dhaliwal JS, Murthy SN, Hyman AL, Nossaman BD et al. Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat. Am J Physiol Heart Circ Physiol 2009;296:H524-H533.
60. Ingram TE, Pinder AG, Bailey DM, Fraser AG, James PE. Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite. Am J Physiol Heart Circ Physiol 2010;298: H331-H339.
61. Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF et al. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med 2004;10:1122-1127.
62. Jung K-H, Chu K, Ko S-Y, Lee S-T, Sinn D-I, Park D-K et al. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury. Stroke 2006;37:2744-2750.
63. Pluta RM, Dejam A, Grimes G, Gladwin MT, Oldfield EH. Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. JAMA 2005;293:1477-1484.
64. Rifkind JM, Nagababu E, Barbiro-Michaely E, Ramasamy S, Pluta RM, Mayevsky A et al. Nitrite infusion increases cerebral blood flow and decreases mean arterial blood pressure in rats: a role for red cell NO. Nitric Oxide 2007;16:448-456.
65. Doyle MP, Pickering RA, DeWeert TM, Hoekstra JW, Pater D. Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. J Biol Chem 1981;256: 12393-12398.
66. Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA et al. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci USA 2000;97:11482-11487.
67. Wilkins RW, Haynes FW, Weiss S. The role of the venous system in circulatory collapse induced by sodium nitrite. J Clin Invest 1937;16:85-91.
68. Joshi MS, Ferguson TB Jr, Han TH, Hyduke DR, Liao JC, Rassaf T et al. Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions. Proc Natl Acad Sci USA 2002;99:10341-10346.
69. Cao Z, Bell JB, Mohanty JG, Nagababu E, Rifkind JM. Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite-induced vasodilation. Am J Physiol Heart Circ Physiol 2009;297:H1494-H503.
70. Bogle RG, Coade SB, Moncada S, Pearson JD, Mann GE. Bradykinin and ATP stimulate L-arginine uptake and nitric oxide release in vascular endothelial cells. Biochem Biophys Res Commun 1991;180:926-932.
71. Garcia JI, Seabra AB, Kennedy R, English AM. Nitrite and nitroglycerin induce rapid release of the vasodilator ATP from erythrocytes: relevance to the chemical physiology of local vasodilation. J Inorg Biochem 2010;104:289-296.
72. Ingram TE, Pinder AG, Bailey DM, Fraser AG, James PE. Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite. Am J Physiol Heart Circ Physiol 2010;298: H331-H339.
73. Geumei A, Issa I, Mahfouz M. Intra-hepatic vascular response to sodium nitrite. Br J Pharmacol 1969;35:456-459.
74. Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int 2000;58:1261-1266.
75. Blum M, Yachnin T, Wollman Y, Chernihovsky T, Peer G, Grosskopf I et al. Low nitric oxide production in patients with chronic renal failure. Nephron 1998;79: 265-268.
76. Scherrer U, Sartori C. Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity. Eur J Endo-crinol 2000;142:315-323.
77. Shiode N, Nakayama K, Morishima N, Yamagata T, Matsuura H, Kajiyama G. Nitric oxide production by coronary conductance and resistance vessels in hypercholes-terolemia patients. Am Heart J 1996;131:1051-1057.
78. Lind L, Lind L. Lipids and endothelium-dependent vasodilation - a review. Lipids 2002;37:1-15.
79. Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet 1983;1:5-10.
80. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336: 1117-1124.
81. Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L et al. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Am J Clin Nutr 2002;76:93-99. (Pubitemid 34686554)
82. Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE et al. The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med 2001; 134:1106-1114.
83. Joshipura KJ, Ascherio A, Manson JE, Stampfer MJ, Rimm EB, Speizer FE et al. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999;282: 1233-1239.
84. Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F et al. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 2010;56:274-281.
85. Nitrate in Vegetables. UK: Ministry of Agriculture Food and Fisheries 1998.
86. Tsuchiya K, Kanematsu Y, Yoshizumi M, Ohnishi H, Kirima K, Izawa Y et al. Nitrite is an alternative source of NO in vivo. Am J Physiol Heart Circ Physiol 2005;288: H2163-H2170.
87. Tsuchiya K, Tomita S, Ishizawa K, Abe S, Ikeda Y, Kihira Y et al. Dietary nitrite ameliorates renal injury in l-NAME-induced hypertensive rats. Nitric Oxide 2010;22: 98-103.
88. Larsen FJ, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E. Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 2006;355:2792-2793.
89. Govoni M, Jansson EA, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide 2008;19:333-337.
90. Petersson J, Carlström M, Schreiber O, Phillipson M, Christoffersson G, Jägare A et al. Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med 2009;46:1068-1075.
91. Lundberg JO, Feelisch M, Bjorne H, Jansson EA, Weitzberg E. Cardioprotective effects of vegetables: is nitrate the answer? Nitric Oxide 2006;15:359-362.
92. Hobbs AJ. Soluble guanylate cyclase: the forgotten sibling. Trends Pharmacol Sci 1997; 18:484-491.
93. Weller R, Pattullo S, Smith L, Golden M, Ormerod A, Benjamin N. Nitric oxide is generated on the skin surface by reduction of sweat nitrate. J Invest Dermatol 1996;107:327-331.
94. Weller R, Price RJ, Ormerod AD, Benjamin N, Leifert C. Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J Appl Microbiol 2001;90:648-652.
95. Minami J, Kawano Y, Ishimitsu T, Yoshimi H, Takishita S. Seasonal variations in office, home and 24 h ambulatory blood pressure in patients with essential hypertension. J Hypertens 1996;14:1421-1425. (Pubitemid 27007810)
96. Matsunaga K, Furchgott RF. Interactions of light and sodium nitrite in producing relaxation of rabbit aorta. J Pharmacol Exp Ther 1989;248:687-695.
97. Mowbray M, McLintock S, Weerakoon R, Lomatschinsky N, Jones S, Rossi AG et al. Enzyme-independent NO stores in human skin: quantification and influence of UV radiation. J Invest Dermatol 2009;129:834-842.
98. Butler AR, Feelisch M. Therapeutic uses of inorganic nitrite and nitrate: from the past to the future. Circulation 2008;117:2151-2159.
99. Tarr L. Transient methemoglobinemia due to ammonium nitrate. Arch Intern Med 1933;51:38-44.
100. Sofos JN, Raharjo S. Curing agents. In: Maga JA, Tu AT, eds. Food Additive Toxicology. New York: Taylor Francis; 1995. p235-268.
101. Spiegelhalder B, Eisenbrand G, Preussmann R. Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol 1976;14:545-548.
102. Tannenbaum SR, Weisman M, Fett D. The effect of nitrate intake on nitrite formation in human saliva. Food Cosmet Toxicol 1976;14:549-552.
103. Williams D. Nitrosation Reactions and the Chemistry of Nitric Oxide. Elsevier; 2004.
104. Deshpande S. Toxicants resulting from food processing. In: Handbook of Food Toxicology. New York: Marcel Decker; 2002. p285-320.
105. WHO. Some N-Nitroso Compounds. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 17. Zurich: World Health Organisation; 1998: http://monographs.iarc.fr/ENG/Monographs/vol17/volume17.pdf (last accessed 13 May 2010).
106. Cohen B, Myant NB. Concentration of salivary iodide: a comparative study. J Physiol 1959;145:595-610.
107. Logothetopoulos JH, Myant NB. Concentration of radio-iodide and 35S-thiocyanate by the salivary glands. J Physiol 1956;134:189-194.
108. Magee P, Barnes J. The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Br J Cancer 1956;10:114-122.
109. Milkowski A, Garg HK, Coughlin JR, Bryan NS. Nutritional epidemiology in the context of nitric oxide biology: a risk-benefit evaluation for dietary nitrite and nitrate. Nitric Oxide 2010;22:110-119.
110. Speijers G, van den Brandt PA. Nitrate. In: Food Additives Series. Geneva: Joint FAO/WHO Expert Committee on Food Additives; 2003.
111. Winter JW, Paterson S, Scobie G, Wirz A, Preston T, McColl KEL. N-nitrosamine generation from ingested nitrate via nitric oxide in subjects with and without gastro-esophageal reflux. Gastroenterology 2007;133:164-174.
112. Autrup H, Stoner GD. Metabolism of N-nitrosamines by cultured human and rat esophagus. Cancer Res 1982;42:1307-1311.
113. Godoy W, Albano RM, Moraes EG, Pinho PRA, Nunes RA, Saito EH et al. CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Carcino-genesis 2002;23:611-616.
114. Harris CC, Autrup H, Stoner GD, Trump BF, Hillman E, Schafer PW et al. Metabolism of benzo(a)pyrene, N-nitrosodimethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus. Cancer Res 1979;39:4401-4406. (Pubitemid 10197595)
115. Swann PF. The possible role of nitrosamines in the link between alcohol consumption and esophageal cancer in man. Toxicol Pathol 1984;12:357-360.
116. Dykhuizen RS, Fraser A, McKenzie H, Golden M, Leifert C, Benjamin N. Helicobac-ter pylori is killed by nitrite under acidic conditions. Gut 1998;42:334-337.
117. Jansson EA, Petersson J, Reinders C, Sobko T, Bjorne H, Phillipson M et al. Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate. Free Radic Biol Med 2007;42:510-518.