Butler, Anthony R. and Feelisch, Martin (2008) Therapeutic uses of inorganic nitrite and nitrate - from the past to the future. Circulation, Vol.117 (No.16). pp. 2151-2159. ISSN 0009-7322

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Abstract

Potential carcinogenic effects, blue baby syndrome, and occasional intoxications caused by nitrite, as well as the suspected health risks related to fertilizer overuse, contributed to the negative image that inorganic nitrite and nitrate have had for decades. Recent experimental studies related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, however, paint a different picture and have led to a renewed interest in the physiological and pharmacological properties of nitrite and nitrate. The range of effects reported suggests that these simple oxyanions of nitrogen have a much richer profile of biological actions than hitherto assumed, and several efforts are currently underway to investigate possible beneficial effects in the clinical arena. We provide here a brief historical account of the medical uses of nitrite and nitrate over the centuries that may serve as a basis for a careful reassessment of the health implications of their exposure and intake and may inform investigations into their therapeutic potential in the future.

Item Type:	Journal Item
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Cardiovascular system -- Diseases -- Treatment, Nitrates -- Therapeutic use, Nitrites -- Therapeutic use, Nitric oxide -- Physiological effect, Nitric oxide -- Therapeutic use
Journal or Publication Title:	Circulation
Publisher:	Lippincott Williams & Wilkins
ISSN:	0009-7322
Date:	22 April 2008
Volume:	Vol.117
Number:	No.16
Number of Pages:	9
Page Range:	pp. 2151-2159
Identification Number:	10.1161/CIRCULATIONAHA.107.753814
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Guthrie Trust, Medical Research Council (Great Britain) (MRC)
References:	1. Mitchell HH, Shonle HA, Grindley HS. The origin of nitrates in urine. J Biol Chem. 1916;24:461– 490. 2. Green LC, Tannenbaum SR, Goldman P. Nitrate synthesis in the germfree and conventional rat. Science. 1981;212:56 –58. 3. Green LC, Ruiz de Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannenbaum SR. Nitrate biosynthesis in man. Proc Natl Acad Sci U S A. 1981;78:7764 –7768. 4. Griess P. Über Metadiamidobenzol als Regens auf Saltpetrige Säure. Chem Ber. 1878;11:624–627. 5. Cruickshank J, Moyes JM. The presence and significance of nitrites in urine. BMJ. 1914;2:712–713. 6. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333:664–666. 7. Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988;27:8706–8711. 8. Gladwin MT, Shelhammer JH, Schechter AN, Pease-Fye ME, Waciawiw MA, Panza JA, Ognibene FP, Cannon RO. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A. 2000;97: 11482–11487. 9. Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007;116: 1821–1831. 10. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7: 156–167. 11. Dezfulian C, Raat N, Shiva S, Gladwin MT. Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics. Cardiovasc Res. 2007;75:327–338. 12. Ingested Nitrates and Nitrites. Lyon, France: International Agency for Research on Cancer; 2007. IARC Monographs volume 94. Available at: http://monographs.iarc.fr/ENG/Meetings/94-nitratenitrite.pdf. Accessed September 4, 2007. 13. Barnum DW. Some history of nitrates. J Chem Ed. 2003;80:1393–1396. 14. Scheele CW. Chemische Abhandlung von der Luft und dem Feuer. Upsala, Sweden: M. Swederus; 1777. 15. Péligot E. Sur l’acide hypoazotique et sur l’acide azoteux. Ann Chim Phys. 1841;2:58–68. 16. Debus AG. The Paracelsian aerial niter. Isis. 1964;55:43– 61. 17. Williams DLH. Nitrosation Reactions and the Chemistry of Nitric Oxide. London, UK: Elsevier; 2004. 18. Ridd JH. Nitrosation, diazotisation and deamination. Quart Rev. 1961; 15:418–436. 19. Magee PN, Barnes JM. The production of primary hepatic malignant tumours in the rat by feeding dimethylnitsoamine. Br J Cancer. 1956; 10:114 –122. 20. Butter W. A Treatise on the Disease Commonly Called Angina Pectoris. London, UK: J. Johnson; 1791. 21. Brunton TL. On the use of nitrite of amyl in angina pectoris. Lancet. 1867;2:97–98. 22. Murrell W. Nitro-glycerine as a remedy for angina pectoris. Lancet. 1879;1:80–81, 113–115. 23. Phillips CDF. Materia Medica, Pharmacology and Therapeutics Inorganic Substances. 2nd ed. London, UK: J&A Churchill; 1894. 24. White WH. Materia Medica Pharmacy, Pharmacology and Therapeutics. London, UK: J&A Churchill; 1899. 25. Fye WB. Nitroglycerin: a homeopathic remedy. Circulation. 1986;73: 21–29. 26. Harrington M. Hypotensive Drugs. London, UK: Pergamon Press; 1956. 27. Bellamy A. The development of nitroglycerine as an explosive. Atti del convegno in celerazione del centenario della morte di Ascanio Sobrero. Turín, Italy: University of Turín; 1989. 28. Fant K. Alfred Nobel: En Biografi. Stockholm, Sweden: Norstedts Förlag; 1991:302. 29. Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerine bioactivation. Proc Natl Acad Sci U S A. 2002;99: 8306–8311. 30. Janero DR, Bryan NS, Saijo F, Dhawan V, Schwalb DJ, Warren MC, Feelisch M. Differential nitros(yl)ation of blood and tissue constituents during glyceryl trinitrate biotransformation in vivo. Proc Natl Acad Sci U S A. 2004;101:16958 –16963. 31. Reichert ET, Mitchell SW. On the physiological action of potassium nitrite. Am J Med Sci. 1880;156:158 –180. 32. Atkinson GA. The physiology of the nitrites and nitro-glycerine. J Anat Physiol. 1888;22:225–239, 351–371. 33. Densham B. The adjuvant action of the lactate ion on the vaso-dilator effect of sodium nitrite. J Physiol. 1927;63:175–179. 34. Hay M. Nitrite of sodium in the treatment of angina pectoris. Practitioner. 1883;30:170–194. 35. Leech DJ. On the duration of the action of medicines. BMJ. 1885;2: 1005–1011. 36. Squibb’s Materia Medica. New York, NY: E.R. Squibb & Sons; 1906. 37. Deusch G, Liepelt A. Die Hautkapillaren beim arteriellen Hochdruck und ihre Beeinflussung durch Nitrite. Deutsches Arch Klin Med. 1928; 160:207–211. 38. Hare HA, Caspari C, Rusby HH. National Standard Dispensatory. Philadelphia, Pa: Lea Bros & Co; 1905. 39. Bennett RG. Materia Medica and Pharmacy for Medical Students. London, UK: HK Lewis; 1921. 40. Blumgarten AS. Textbook of Materia Medica and Therapeutics. New York, NY: MacMillan; 1934. 41. Modin A, Bjorne H, Herulf M, Alving K, Weitzberg E, Lundberg JO. Nitrite-derived nitric oxide: a possible mediator of “acidic-metabolic” vasodilation. Acta Physiol Scand. 2001;171:9 –16. 42. Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995;1: 804–809. 43. Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003;9:1498 –1505. 44. Angelo M, Singel DJ, Stamler JS. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. Proc Natl Acad Sci U S A. 2006;103:8366–8371. 45. Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG, Gladwin MT. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004;10: 1122–1127. 46. Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet. 2002;360:141–143. 47. Beier S, Classen HG, Loeffler K, Schumacher E, Thöni H. Antihypertensive effect of oral nitrite uptake in the spontaneously hypertensive rat. Arzneimittelforschung. 1995;45:258 –261. 48. Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci U S A. 2001;98:12814 –12819. 49. Dalsgaard T, Simonsen U, Fago A. Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities. Am J Physiol Heart Circ Physiol. 2007;292: H3072–H3078. 50. Furchgott RF, Bhadrakom. Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther. 1953;108:129 –143. 51. Farrari R, Cargoni A, Bernocchi P, Pasini E, Curello S, Ceconi C, Ruigrok TJC. Metabolic adaptation during a sequence of no-flow and low-flow ischemia. Circulation. 1996;94:2587–2596. 52. Samlouilov A, Kuppusamy P, Zweier JI. Evaluation of the magnitude and rate of nitric oxide production from nitrite in biological systems. Arch Biochem Biophys. 1998;357:1–7. 53. Butler AR, Ridd JH. Formation of nitric oxide from nitrous acid in ischemic tissue and skin. Nitric Oxide. 2004;10:20 –24. 54. Webb A, Bond R, McClean P, Uppal R, Benjamin N, Ahluwalia A. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemic-reperfusion damage. Proc Natl Acad Sci U S A. 2004;101:13683–13688. 55. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch M. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol. 2005;1:290 –297. 56. Granville AB. Further Observations on the Internal Use of the Hydrocyanic (Prussic) Acid. London, UK: Butgess & Hill; 1820. 57. Magendie F. Sur l’emploi de l’acide prussique dans le traitement de plusieurs maladies de poitrine, et particulièrement dans la phtisie pulmonaire. Ann Chim Phys. 1817;6:347–360. 58. Commoner B. Cyanide inhibition as a means of elucidating the mechanism of cellular respiration. Bio Rev (Cambridge Phil Soc). 1940; 15:168 –201. 59. Keilin D, Hartree EF. Cytochrome c and cytochrome oxidase. Proc Royal Soc London Series B. 1939;127:167–191. 60. Kobert R. U¨ ber Cyanmetha¨moglobin und den Nachweis der Blausa¨ure. Stuttgart, Enke: Germany; 1891; Cited by: Keilin D. The History of Cell Respiration and Cytochrome. Cambridge, UK: CUP; 1966. 61. Hug E. Accion del nitrite de sodio del hiposulfate de sodio en el tratamiento de la intoxication provocada por el ciannuro de potassio en al conejo. Rev Soc Argent Biol. 1932;3:270 –276. 62. Viana C, Cagnoli H, Cendan J. L’action du nitrite de sodium dans l’intoxication par les cyanures. C R Seances Soc Biol Fil. 1934;115: 1649–1651. 63. Matthew H, Lawson AAH. Treatment of Common Acute Poisonings. 4th ed. Edinburgh, Scotland: Churchill Livingstone; 1979. 64. Cucinell SA, Groff WA, Vick JA, Weger N. Treatment of cyanide poisoning. Fed Proc. 1974;33:234. Abstract. 65. Isom GE, Way JL. Lethality of cyanide in the absence of inhibition of liver cytochrome oxidase. Biochem Pharmacol. 1976;25:605– 608. 66. Baskin SI, Froehlich HL, Groff WA. The dissociation of reversal of cyanide (CN) toxicity and methemoglobin formation by nitrite (N) in the isolated heart. Fed Proc. 1986;45:196. Abstract. 67. Ali MY, Ping CY, Mok YY, Ling L, Whiteman M, Bhatia M, Moore PK. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br J Pharmacol. 2006;149: 625–634. 68. Smith RP, Gosselin RE. Hydrogen sulfide poisoning. J Occup Med. 1979;21:93–97. 69. Smith RP, Kruszyna R, Kruszyna H. Management of acute sulfide poisoning: effects of oxygen, thiosulfate, and nitrite. Arch Environ Health. 1976;31:166 –169. 70. Beck JF, Bradbury CM, Connors AJ, Donini JC. Nitrite as antidote for acute hydrogen sulfide intoxication? Am Ind Hyg Assoc J. 1981;42: 805–809. 71. Scheler W, Kabisch R. On the antagonistic alteration of acute H2S poisoning in mice with methemoglobin forming agents. Acta Biol Med Ger. 1963;11:194 –199. 72. Stine RJ, Slosberg B, Beacham BE. Hydrogen sulfide intoxication: a case report and discussion of treatment. Ann Intern Med. 1976;85: 756–758. 73. Chen KK, Rose CL. Nitrite and thiosulfate therapy in cyanide poisoning. JAMA. 1952;149:113–119. 74. Law WT. Sodium nitrite in the treatment of epilepsy. Practitioner. 1882;28:420–424. 75. Ringer S, Murrell W. Nitrite of sodium as a toxic agent. Lancet. 1883; 2:766 –767. 76. van Grinsven HJM, Ward MH, Benjamin N, de Kok TM. Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water? Environ Health. 2006;5:26 –30. 77. Lundberg JO, Weitzberg E, Cole JA, Benjamin N. Nitrate, bacteria and human health. Nat Rev Microbiol. 2004;2:593– 602. 78. 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. 79. Yoon SS, Coakley R, Lau GW, Lymar SV, Gaston B, Karabulut AC, Hennigan RF, Hwang SH, Buettner G, Schurr MJ, Mortensen JE, Burns JL, Speert D, Boucher RC, Hassett DJ. Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest. 2006;116:436–446. 80. 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. 81. Tucker AT, Pearson RM, Cooke ED, Benjamin N. Effect of nitric-oxidegenerating system on microcirculatory blood flow in skin of patients with severe Raynaud’s syndrome: a randomised trial. Lancet. 1999;354: 1670–1675. 82. Khan F, Pearson RJ, Newton DJ, Belch JJF, Butler AR. Chemical synthesis and microvascular effects of new nitric oxide donors in humans. Clin Sci. 2003;195:577–584. 83. Weller R, Finnen MJ. The effects of topical treatment with acidified nitrite on wound healing in normal and diabetic mice. Nitric Oxide. 2006;15:395–399. 84. Ts’ao TC, Ho PY, Needham J. An early mediaeval Chinese alchemical text on aqueous solutions. Ambix. 1959;7:122–155. 85. Butler AR, Moffett J. In: Lo EY, Cullen C, eds. Medieval Chinese Medicine: The Dunhuang Medical Manuscripts. London, UK: Routledge; 2004. 86. Duncan C, Dougall H, Johnson P, Green S, Brogan R, Leifert C, Smith L, Golden M, Benjamin N. Chemical generation of nitric oxide from the enterosalivary circulation of dietary nitrate. Nat Med. 1995;1:546 –551. 87. Pietsch G. Dissertation sur la Generation du Nitre. Berlin, Germany: Chez Haude et Spener; 1746. 88. Postgate J. Nitrogen Fixation. 3rd ed. Cambridge, UK: CUP; 1998. 89. Challoner T. A Short Discourse on the Most Rare and Excellent Vertue of Nitre. London, UK; G Dewes; 1584. 90. Benjamin N, Pattullo S, Weller R, Smith L, Omerod A. Wound licking and nitric oxide. Lancet. 1997;349:1776. 91. Pearse F. The treatment of paroxysmal nerve disorders. Practitioner. 1891;46:29 –32. 92. Cassan S. Relieving affections of the lungs or chest. UK Patent 2524; 1868. 93. Encyclopædia Britannica. Vol. XXIV, 11th ed. Cambridge, UK: CUP; 1911:94. 94. Dispensatory of the United States of America. 21st ed. Philadelphia, Pa: JB Lippincott; 1926. 95. Oza TM. Thermal decomposition of sodium and potassium nitrites. J Indian Chem Soc. 1945;22:173–180. 96. Ziment I. History of the treatment of chronic bronchitis. Respiration. 1991;58(suppl 1):37– 42. 97. Willis T. Pharmaceutice Rationalis: Or an Exercitation of the Medicines in Humane Bodies. London, UK; T. Dring, C. Harper, and J. Leigh; 1697. 98. Jörg JCG. Materialien zu einer künftigen Heilmittellehre durch Versuche der Arzneyen an gesunden Menschen gewonnen u. gesammelt. Leipzig, Germany: Carl Cnobloch; 1825. 99. Hiatt EP. Comparison of the diuretic effects of nitrate salts with other diuretic agents. Am J Physiol. 1957;189:173–176. 100. Cahn A. Die Magenverdauung im Chlorhunger. Ztschr F Physiol Chem. 1886;10:522–535. 101. Greene I, Hiatt EP. Renal excretion of nitrate and its effect on excretion of sodium and chloride. Am J Physiol. 1954;180:179 –182. 102. Keith NM, Whelan M, Bannick EG. The action and excretion of nitrates. Arch Intern Med. 1930;46:797– 832. 103. Beck EG. Toxic effects from bismuth subnitrate: with reports of cases to date. JAMA. 1909;52:14 –18. 104. Alexander W. William Alexander’s Medizinische Versuche und Erfahrungen. Leipzig, Germany: A.d.E.; 1773. 105. Eustermann GB, Keith NM. Transient methemoglobinemia following administration of ammonium nitrate. Med Clin North Am. 1929;12: 1489–1496. 106. Tarr L. Transient methemoglobinemia due to ammonium nitrate. Arch Intern Med. 1933;51:38–44. 107. 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. 108. Humphreys SD, Routledge PA. The toxicology of silver nitrate. Adverse Drug React Toxicol Rev. 1998;17:115–143. 109. Archer DL. Evidence that ingested nitrate and nitrite are beneficial to health. J Food Prot. 2002;65:872– 875. 110. Addiscott TM, Benjamin N. Are you taking your nitrate? Food Sci Technol Today. 2000;14:59–61. 111. L’Hirondel JJ, L’Hirondel J-L. Nitrate and Man: Toxic, Harmless or Beneficial? Oxford, UK: CABI Publishing; 2002. 112. Suschek CV, Schewe T, Sies H, Kroncke KD. Nitrite, a naturally occurring precursor of nitric oxide that acts like a “prodrug.” Biol Chem. 2006;387:499 –506. 113. Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, Macarthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT. Nitrite augments tolerance to ischemia/ reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med. 2007;204:2089 –2102. 114. Lundberg JO, Feelisch M, Bjorne H, Jansson EA, Weitzberg E. Cardioprotective effects of vegetables: is nitrate the answer? Nitric Oxide. 2006;15:359 –362. 115. Richardson G, Hicks SL, O’Byrne S, Frost MT, Moore K, Benjamin N, McKnight GM. The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans. Nitric Oxide. 2002;7:24 –29. 116. 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. 117. Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol. 2007;191:59–66. 118. Erzurum SC, Ghosh S, Janocha AJ, Xu W, Bauer S, Bryan NS, Tejero T, Hemann C, Hille R, Stuehr DJ, Feelisch M, Beall CM. Higher blood flow and circulating nitric oxide products offset high-altitude hypoxia among Tibetans. Proc Natl Acad U S A. 2007;104:17593–17598.
URI:	http://wrap.warwick.ac.uk/id/eprint/30187

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