Skip to main content
SpringerLink
Log in

In vivo detection of nitric oxide distribution in mice

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

This paper discusses in vivo detection of nitric oxide (NO) distribution in endotoxin-treated mice using L-band (1.1 GHz) electron paramagnetic resonance spectroscopy (EPR) in combination with the hydrophilic NO trapping complex: N-methyl-D-glucamine dithiocarbamate and iron (MGD-Fe). MGD-Fe-NO complex is found in the upper abdomen (liver region), lower abdomen (kidney and urinary bladder) and head region of ICR mice. Experiments with nitric oxide synthase (NOS) inhibition and 15N-labeled L-arginine as NOS substrate verify the origin of trapped NO from L-arginine. However, contribution from a 'nonenzymatic' NO generation pathway can not be ruled out. This paper further examines potential artifacts, which may arise in experiments using dithiocarbamate-iron complexes as NO trapping agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Komarov A, Mattson D, Jones MM, Singh PK, Lai C-S: In vivo spin trapping of nitric oxide in mice. Biochem Biophys Res Commun 195: 1191–1198, 1993

    Article  PubMed  Google Scholar 

  2. Lai C-S, Komarov AM: Spin trapping of nitric oxide produced in vivo in septic shock mice. FEBS Lett 345: 120–124, 1994

    Article  PubMed  Google Scholar 

  3. Komarov AM, Lai C-S: Detection of nitric oxide production in mice by spin trapping electron paramagnetic resonance spectroscopy. Biochim Biophys Acta 1272: 29–36, 1995

    PubMed  Google Scholar 

  4. Quaresima V, Takehara H, Tsushima K, Ferrari M, Utsumi H: In vivo detection of mouse liver nitric oxide generation by spin trapping electron paramagnetic resonance spectroscopy. Biochem Biophys Res Commun 221: 729–734, 1996

    PubMed  Google Scholar 

  5. Fujii H, Koscielniak J, Berliner LJ: Determination and characterization of nitric oxide generation in mice by in vivo L-band EPR spectroscopy. Magn Reson Med 38: 565–568, 1997

    PubMed  Google Scholar 

  6. Komarov AM: In vivo on-line detection of NO distribution in endotoxin-treated mice by L-band ESR. Cell Mol Biol 46: 1329–1336, 2000

    PubMed  Google Scholar 

  7. Yoshimura T, Yokoyama H, Fujii S, Takayama F, Oikawa K, Kamada H: In vivo EPR detection and imaging of endogenous nitric oxide in lipopolysaccharide-treated mice. Nature Biotechnol 14: 992–994, 1996

    Article  Google Scholar 

  8. Berliner LJ, Koscielniak J: Low-frequency EPR spectrometers: Lband. In: G. Eaton, S. Eato, K. Ohno (eds). EPR Imaging and In Vivo EPR. CRC Press, Boca Raton, FL, 1991, pp 65–75

    Google Scholar 

  9. Fujii H, Wan X, Zhong J, Berliner LJ, Yoshikawa K: In vivo imaging of spin-trapped nitric oxide in rats with septic shock: MRI spin trapping. Magn Res Med 42: 235–239, 1999

    Google Scholar 

  10. Mülsch A, Lurie DJ, Seimenis I, Fichtlscherer B, Foster M: Detection of nitrosyl-iron complexes by proton-electron-double-resonance imaging. Free Rad Biol Med 27: 636–646, 1999

    PubMed  Google Scholar 

  11. Shinobu LA, Jones SC, Jones MM: Sodium N-methyl-D-glucamine dithiocarbamate and cadmium intoxication. Acta Pharmacol Toxicol 54: 189–194, 1984

    Google Scholar 

  12. Lai C-S, Komarov AM: Dithiocarbamate spin traps for in vivo detection of nitric oxide produced in mice. In: H. Ohya-Nishiguchi, L. Packer (eds). Bioradicals Detected by ESR Spectroscopy. Birkhauser Verlag, Basel, 1995, pp 163–171

    Google Scholar 

  13. Froncisz W, Oles T, Hyde JC: Murine L-band ESR loop-gap resonator. J Magn Reson 82: 109–114, 1989

    Google Scholar 

  14. Subczynski WK, Lukiewicz S, Hyde JS: Murine in vivo L-band ESR spin-label oximetry with a loop-gap resonator. Magn Reson Med 3: 747–745, 1986

    PubMed  Google Scholar 

  15. Misik V, Riesz P: Nitric oxide formation by ultrasound in aqueous solutions. J Phys Chem 100: 17986–17994, 1996

    Google Scholar 

  16. Pou S, Tsai P, Porasuphatana S, Halpern H, Chandramouli GVR, Barth ED, Rosen GM: Spin trapping of nitric oxide by ferrochelates: Kinetic and in vivo pharmacokinetic studies. Biochim Biophys Acta 1427: 216–226, 1999

    PubMed  Google Scholar 

  17. Fujii S, Yoshimura T: A new trend in iron-dithiocarbamate complexes: As an endogenous NO trapping agent. Coord Chem Rev 198: 89–99, 2000

    Google Scholar 

  18. Paschenko SV, Khramtsov VV, Skatchkov MP, Plysnin VF, Bassenge E: EPR and laser flash photolysis studies of the reaction of nitric oxide with water soluble NO trap Fe(II)-proline-dithiocarbamate complex. Biochem Biophys Res Commun 225: 577–584, 1996

    PubMed  Google Scholar 

  19. Wong M-L, Rettori V, Al-Shekhlee A, Bongiorno PB, Canteros G, McCann SM, Gold PW, Licinio J: Inducible nitric oxide synthase gene expression in the brain during systemic inflammation. Nature Med 2: 581–584, 1996

    PubMed  Google Scholar 

  20. Mikoyan VD, Voevodskaya NV, Kubrina LN, Malenkova IV, Vanin AF: The influence of antioxidants and cycloheximide on the level of nitric oxide in the livers of mice in vivo. Biochim Biophys Acta 1269: 19–24, 1995

    PubMed  Google Scholar 

  21. Yoshimura T, Fujii S, Yokoyama H, Kamada H: In vivo electron paramagnetic resonance imaging of NO-bound iron complex in a rat head. Chem Lett 4: 309–310, 1995

    Google Scholar 

  22. Fujii S, Yasuhiro S, Yoshimura T, Kamada H: In vivo three-dimensional EPR imaging of nitric oxide production from isosorbide dinitrate in mice. Am J Physiol 274: G857–G862, 1998

    PubMed  Google Scholar 

  23. Lecour S, Maupoil V, Siri O, Tabard A, Rochette L: Electron spin resonance detection of nitric oxide generation in major organs from LPS-treated rats. J Cardiovasc Pharmacol 33: 78–85, 1999

    PubMed  Google Scholar 

  24. James PE, Liu KJ, Swartz HM: Direct detection of tissue nitric oxide in septic mice. In: A. Hudetz, D. Bruley (ed). Advances in Experimental Medicine and Biology. Plenum Press, New York, 1998, pp 181–187

    Google Scholar 

  25. Tsuchiya K, Jiang J-J, Yoshizumi M, Tamaki T, Houchi H, Minakuchi K, Fukuzawa K, Mason RP: Nitric oxide-forming reactions of the water-soluble nitric oxide spin-trapping agent MGD. Free Radic Biol Med 27: 347–355, 1999

    PubMed  Google Scholar 

  26. Tsuchiya K, Mason RP: NO-forming reactions between the iron-N-methyl-D-glucamine dithiocarbamate complex and nitrite. J Biol Chem 275: 1551–1556, 2000

    PubMed  Google Scholar 

  27. Paya D, Maupoil V, Schott C, Rochette L, Stoclet J-C: Temporal relationships between levels of circulating NO derivatives, vascular NO production and hyporeactivity to noradrenaline induced by endotoxin in rats. Cardiovasc Res 30: 952–959, 1995

    PubMed  Google Scholar 

  28. Wennmalm A, Benthin G, Petersson A-S: Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin. Br J Pharmacol 106: 507–508, 1992

    PubMed  Google Scholar 

  29. Kim Y-M, Lancaster JR Jr: Tetrahydrobiopterin-dependent nitrite oxidation to nitrate in isolated rat hepatocytes. FEBS Lett 332: 255–259, 1993

    PubMed  Google Scholar 

  30. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR: Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126: 131–138, 1982

    PubMed  Google Scholar 

  31. Kuppusamy P, Wang P, Samoilov A, Zweier JL: Spatial mapping of nitric oxide generation in the ischemic heart using electron paramagnetic resonance imaging. Magn Reson Med 36: 212–218, 1996

    PubMed  Google Scholar 

  32. Benjamin N, O'Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H: Stomach NO synthesis. Nature (London) 368: 502, 1994

    Google Scholar 

  33. Cornforth D: Role of nitric oxide in treatment of foods. In: J. Lancaster (ed). Nitric Oxide: Principles and Actions. Academic Press, San Diego, 1996, pp 259–287

    Google Scholar 

  34. Reutov VP, Sorokina EG: NO-synthase and nitrite-reductase components of nitric oxide cycle. Biochemistry (Moscow) 63: 874–884, 1998

    Google Scholar 

  35. Komarov AM: Chemistry and biology of nitric oxide. In: L. Berliner (ed). Biological Magnetic Resonance. Kluwer, New York, 2001 (in press)

    Google Scholar 

  36. Vanin AF, Liu X, Samouilov A, Stukan RA, Zweier JL: Redox properties of iron-dithiocarbamates and their nitrosyl derivatives: Implications for their use as traps of nitric oxide in biological systems. Biochim Biophys Acta 1474: 365–377, 2000

    PubMed  Google Scholar 

  37. Komarov AM, Wink DA, Feelisch M, Schmidt HHHW: Electron-paramagnetic resonance spectroscopy using N-methyl-D-glucamine dithiocarbamate iron cannot discriminate between nitric oxide and nitroxyl: Implications for the detection of reaction products for nitric oxide synthase. Free Radic Biol Med 28: 739–742, 2000

    PubMed  Google Scholar 

  38. Bazylinski DA, Hollocher TC: Metmyoglobin and methemoglobin as efficient traps for nitrosyl hydride (nitroxyl) in neutral aqueous solution. J Am Chem Soc 107: 7982–7986, 1985

    Google Scholar 

  39. Bazylinski DA, Goretski J, Hollocher TC: On the reaction of tri-oxodinitrate (II) with hemoglobin and myoglobin. J Am Chem Soc 107: 7986–7989, 1985

    Google Scholar 

  40. Xia Y, Cardounel AJ, Vanin AF, Zweier JL: Electron paramagnetic resonance spectroscopy with N-methyl-D-glucamine dithiocarbamate iron complexes distinguishes nitric oxide and nitroxyl anion in a redox-dependent manner: Applications in identifying nitrogen monoxide products from nitric oxide synthase. Free Radic Biol Med 29: 793–797, 2000

    PubMed  Google Scholar 

  41. Nakamura M, Nakamura S: Conversion of metmyoglobin to NO myoglobin in the presence of nitrite and reductants. Biochim Biophys Acta 1289: 329–335, 1996

    PubMed  Google Scholar 

  42. Mülsch A, Schray-Utz B, Mordvintcev PI, Hauschildt S, Busse R: Diethyldithiocarbamate inhibits induction of macrophage NO synthase. FEBS Lett 321: 215–218, 1993

    PubMed  Google Scholar 

  43. Komarov AM, Mattson DL, Mak IT, Weglicki WB: Iron attenuates nitric oxide level and iNOS expression in endotoxin-treated mice. FEBS Lett 424: 253–256, 1998

    PubMed  Google Scholar 

  44. Komarov AM, Mak IT, Weglicki WB: Iron potentiates nitric oxide scavenging by dithiocarbamates in tissue of septic shock mice. Biochim Biophys Acta 1361: 229–234, 1997

    PubMed  Google Scholar 

  45. Yoneyama H, Kosaka H, Ohnishi T, Kawazoe T, Mizoguchi K, Ichikawa Y: Reaction of neuronal nitric oxide synthase with the nitric oxide spin-trapping agent, iron complexed with N-dithiocarboxysarcosine. Eur J Biochem 266: 771–777, 1999

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Experimental Medicine, The George Washington University Medical Center, Washington, DC, USA

    Andrei M. Komarov

Authors
  1. Andrei M. Komarov
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Komarov, A.M. In vivo detection of nitric oxide distribution in mice. Mol Cell Biochem 234, 387–392 (2002). https://doi.org/10.1023/A:1015911216137

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015911216137

Search

Navigation