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. 1987 Aug;73:201–205. doi: 10.1289/ehp.8773201

Biotransformation of nitric oxide.

K Yoshida 1, K Kasama 1
PMCID: PMC1474568  PMID: 3665863

Abstract

Previous investigations into the health effects of nitrogen oxides (NOx) have mostly been conducted with special reference to nitrogen dioxide (NO2) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. We carried out a study on NO by exposing rats and mice to 15NO or administering 15N-nitrite and 15N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO. The results of our study and previous findings led us to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrite (NO2-) and nitrate (NO3-) are generated. Major quantities of NO3- are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO2-. Part of this NO2- is converted to N2 gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH3) through NO2-, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Case G. D., Dixon J. S., Schooley J. C. Interactions of blood metalloproteins with nitrogen oxides and oxidant air pollutants. Environ Res. 1979 Oct;20(1):43–65. doi: 10.1016/0013-9351(79)90084-7. [DOI] [PubMed] [Google Scholar]
  2. Dooley M. M., Pryor W. A. Free radical pathology: inactivation of human alpha-1-proteinase inhibitor by products from the reaction of nitrogen dioxide with hydrogen peroxide and the etiology of emphysema. Biochem Biophys Res Commun. 1982 Jun 15;106(3):981–987. doi: 10.1016/0006-291x(82)91807-1. [DOI] [PubMed] [Google Scholar]
  3. Friedman M. A., Greene E. J., Epstein S. S. Rapid gastric absorption of sodium nitrite in mice. J Pharm Sci. 1972 Sep;61(9):1492–1494. doi: 10.1002/jps.2600610937. [DOI] [PubMed] [Google Scholar]
  4. GREENE I., HIATT E. P. Behavior of the nitrate ion in the dog. Am J Physiol. 1954 Mar;176(3):463–467. doi: 10.1152/ajplegacy.1954.176.3.463. [DOI] [PubMed] [Google Scholar]
  5. Goldstein E., Peek N. F., Parks N. J., Hines H. H., Steffey E. P., Tarkington B. Fate and distribution of inhaled nitrogen dioxide in rhesus monkeys. Am Rev Respir Dis. 1977 Mar;115(3):403–412. doi: 10.1164/arrd.1977.115.3.403. [DOI] [PubMed] [Google Scholar]
  6. Goldstein E., Peek N. F., Parks N. J., Hines H. H., Steffey E. P., Tarkington B. Fate and distribution of inhaled nitrogen dioxide in rhesus monkeys. Am Rev Respir Dis. 1977 Mar;115(3):403–412. doi: 10.1164/arrd.1977.115.3.403. [DOI] [PubMed] [Google Scholar]
  7. Hawksworth G. M., Hill M. J. Bacteria and the N-nitrosation of secondary amines. Br J Cancer. 1971 Sep;25(3):520–526. doi: 10.1038/bjc.1971.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holt P. G., Finlay-Jones L. M., Keast D., Papadimitrou J. M. Immunological function in mice chronically exposed to nitrogen oxides (NOx). Environ Res. 1979 Jun;19(1):154–162. doi: 10.1016/0013-9351(79)90043-4. [DOI] [PubMed] [Google Scholar]
  9. Illing J. W., Miller F. J., Gardner D. E. Decreased resistance to infection in exercised mice exposed to NO2 and O3. J Toxicol Environ Health. 1980 Jul;6(4):843–851. doi: 10.1080/15287398009529902. [DOI] [PubMed] [Google Scholar]
  10. KILGORE L., ALMON L., GIEGER M. The effects of dietary nitrate on rabbits and rats. J Nutr. 1959 Sep;69:39–44. doi: 10.1093/jn/69.1.39. [DOI] [PubMed] [Google Scholar]
  11. Kobayashi T., Miki N., Oda H., Akiyama M., Kubota K., Takahashi H., Nagasawa S. Effect of nitrogen dioxide exposure on cyclic GMP in rat lung. Toxicol Lett. 1982 Sep;13(1-2):35–41. doi: 10.1016/0378-4274(82)90136-9. [DOI] [PubMed] [Google Scholar]
  12. Kon K., Maeda N., Shiga T. Effect of nitric oxide on the oxygen transport of human erythrocytes. J Toxicol Environ Health. 1977 May;2(5):1109–1113. doi: 10.1080/15287397709529508. [DOI] [PubMed] [Google Scholar]
  13. Kosaka H., Imaizumi K., Imai K., Tyuma I. Stoichiometry of the reaction of oxyhemoglobin with nitrite. Biochim Biophys Acta. 1979 Nov 23;581(1):184–188. doi: 10.1016/0005-2795(79)90235-6. [DOI] [PubMed] [Google Scholar]
  14. Miki N., Kawabe Y., Kuriyama K. Activation of cerebral guanylate cyclase by nitric oxide. Biochem Biophys Res Commun. 1977 Apr 25;75(4):851–856. doi: 10.1016/0006-291x(77)91460-7. [DOI] [PubMed] [Google Scholar]
  15. Mirvish S. S., Wallcave L., Eagen M., Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science. 1972 Jul 7;177(4043):65–68. doi: 10.1126/science.177.4043.65. [DOI] [PubMed] [Google Scholar]
  16. Oda H., Kusumoto S., Nakajima T. Nitrosyl-hemoglobin formation in the blood of animals exposed to nitric oxide. Arch Environ Health. 1975 Sep;30(9):453–456. doi: 10.1080/00039896.1975.10666749. [DOI] [PubMed] [Google Scholar]
  17. Oda H., Tsubone H., Suzuki A., Ichinose T., Kubota K. Alterations of nitrite and nitrate concentrations in the blood of mice exposed to nitrogen dioxide. Environ Res. 1981 Aug;25(2):294–301. doi: 10.1016/0013-9351(81)90031-1. [DOI] [PubMed] [Google Scholar]
  18. Postlethwait E. M., Mustafa M. G. Fate of inhaled nitrogen dioxide in isolated perfused rat lung. J Toxicol Environ Health. 1981 Jun;7(6):861–872. doi: 10.1080/15287398109530029. [DOI] [PubMed] [Google Scholar]
  19. Pryor W. A. Free radical biology: xenobiotics, cancer, and aging. Ann N Y Acad Sci. 1982;393:1–22. doi: 10.1111/j.1749-6632.1982.tb31228.x. [DOI] [PubMed] [Google Scholar]
  20. Richters A., Richters V. A new relationship between air pollutant inhalation and cancer. Arch Environ Health. 1983 Mar-Apr;38(2):69–75. doi: 10.1080/00039896.1983.10543983. [DOI] [PubMed] [Google Scholar]
  21. Sagai M., Ichinose T., Oda H., Kubota K. Studies on biochemical effects of nitrogen dioxide: I. Lipid peroxidation as measured by ethane exhalation of rats exposed to nitrogen dioxide. Lipids. 1981 Jan;16(1):64–67. doi: 10.1007/BF02534923. [DOI] [PubMed] [Google Scholar]
  22. Schneider N. R., Yeary R. A. Nitrite and nitrate pharmacokinetics in the dog, sheep, and pony. Am J Vet Res. 1975 Jul;36(7):941–947. [PubMed] [Google Scholar]
  23. Tannenbaum S. R., Fett D., Young V. R., Land P. D., Bruce W. R. Nitrite and nitrate are formed by endogenous synthesis in the human intestine. Science. 1978 Jun 30;200(4349):1487–1489. doi: 10.1126/science.663630. [DOI] [PubMed] [Google Scholar]
  24. WANG L. C., GARCIA-RIVERA J., BURRIS R. H. Metabolism of nitrate by cattle. Biochem J. 1961 Nov;81:237–242. doi: 10.1042/bj0810237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whelan M. The nitrate content of animal tissues, and the fate of ingested nitrate. Biochem J. 1935 Mar;29(3):782–787. doi: 10.1042/bj0290782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Witter J. P., Gatley S. J., Balish E. Distribution of nitrogen-13 from labeled nitrate (13No3-) in humans and rats. Science. 1979 Apr 27;204(4391):411–413. doi: 10.1126/science.441728. [DOI] [PubMed] [Google Scholar]
  27. Yoshida K., Kasama K., Kitabatake M., Imai M. Biotransformation of nitric oxide, nitrite and nitrate. Int Arch Occup Environ Health. 1983;52(2):103–115. doi: 10.1007/BF00405415. [DOI] [PubMed] [Google Scholar]
  28. Yoshida K., Kasama K., Kitabatake M., Okuda M., Imai M. Metabolic fate of nitric oxide. Int Arch Occup Environ Health. 1980;46(1):71–77. doi: 10.1007/BF00377461. [DOI] [PubMed] [Google Scholar]

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