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NO adducts in mammalian red blood cells: too much or too little?

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References

  1. McMahon, T.J. et al. Nitric oxide in the human respiratory cycle. Nat. Med. 8, 711–717 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Rassaf, T. et al. Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical study on the fate of NO in human blood. Circ. Res. 91, 470–477 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Jia, L., Bonaventura, C., Bonaventura, J. & Stamler, J.S. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 380, 221–226 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Feelisch, M. et al. Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo. FASEB J. 16, 1775–1785 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Rassaf, T., Bryan, N.S., Kelm, M. & Feelisch, M. Concomitant presence of N-nitroso and S-nitroso proteins in human plasma. Free Radic. Biol. Med. 33, 1590–1596 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Wennmalm, A. et al. Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ. Res. 73, 1121–1127 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Cantilena, L.R. et al. Nitric oxide hemoglobin in patients receiving nitroglycerin as detected by electron paramagnetic resonance spectroscopy. J. Lab. Clin. Med. 120, 902–907 (1992).

    PubMed  Google Scholar 

  8. Miranda J.J. Highly reactive cysteine residues in rodent hemoglobins. Biochem. Biophys. Res. Commun. 275, 517–523 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Rossi, R. et al. Fast-reacting thiols in rat hemoglobins can intercept damaging species in erythrocytes more efficiently than glutathione. J. Biol. Chem. 273, 19198–19206 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Hobbs, A.J., Gladwin, M.T., Patel, R.P., Williams, D.L. & Butler, A.R. Haemoglobin: NO transporter, NO inactivator or NOne of the above? Trends Pharmacol. Sci. 23, 406–411 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Luchsinger, B.P. et al. Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the β subunits. Proc. Natl. Acad. Sci. USA 100, 461–466 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mamone, G., Sannolo, N., Malorni, A. & Ferranti, P. In vitro formation of S-nitrosohemoglobin in red cells by inducible nitric oxide synthase. FEBS Lett. 462, 241–245 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. Roccatello, D. et al. Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in hemodialysis. Nephrol. Dial. Transplant 12, 292–297 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. Kirima, K. et al. Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO. Am. J. Physiol. Heart Circ. Physiol., 27 March 2003 (DOI 10.1152/ajpheart. 01010.2002).

  15. Takahashi, Y. et al. Nitrosyl hemoglobin in blood of normoxic and hypoxic sheep during nitric oxide inhalation. Am. J. Physiol. Heart Circ. Physiol. 274, H349–H357 (1998).

    Article  CAS  Google Scholar 

  16. Gonzalez-Alonso, J., Richardson, R.S. & Saltin, B. Exercising skeletal muscle blood flow in humans responds to reduction in arterial oxyhaemoglobin, but not to altered free oxygen. J. Physiol. 530, 331–341 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Stamler, J.S. et al. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276, 2034–2037 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. Dietrich, H.H., Ellsworth, M.L., Sprague, R.S. & Dacey, R.G. Red blood cell regulation of microvascular tone through adenosine triphosphate. Am. J. Physiol. Heart Circ. Physiol. 278, H1294–H1298 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Gorczynski, R.J. & Duling, B.R. Role of oxygen in arteriolar functional vasodilation in hamster striated muscle. Am. J. Physiol. 235, H505–H515 (1978).

    CAS  PubMed  Google Scholar 

  20. Kashiwagi, S., Kajimura, M., Yoshimura, Y. & Suematsu, M. Nonendothelial source of nitric oxide in arterioles but not in venules: alternative source revealed in vivo by diaminofluorescein microfluorography. Circ. Res. 91, e55–e64 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Gladwin, M.T. et al. Relative role of heme nitrosylation and β-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. Proc. Natl. Acad. Sci. USA 97, 9943–9948 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pawloski, J.R., Hess, D.T. & Stamler, J.S. Export by red blood cells of nitric oxide bioactivity. Nature 409, 622–626 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Gow, A.J. & Stamler, J.S. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature 391, 169–173 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. McMahon, T.J., Stone, A.E., Bonaventura, J., Singel, D.J. & Stamler, J.S. Functional coupling of oxygen-binding and vasoactivity in S-nitrosohemoglobin. J. Biol. Chem. 275, 16738–16745 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Herold, S. & Rock, G. Reactions of deoxy-, oxy-, and methemoglobin with nitrogen monoxide. Mechanistic studies of the S-nitrosothiol formation under different mixing conditions. J. Biol. Chem. 278, 6623–6634 (2003).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are indebted to T. Bunton, H. Hanley and H. Price for skillful technical assistance. This work was supported in part by US National Institutes of Health grant HL69029 (to M.F.) and funds from the Deutsche Forschungsgemeinschaft (Ra 969/1-1 to T.R.).

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Correspondence to Martin Feelisch.

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Rassaf, T., Bryan, N., Maloney, R. et al. NO adducts in mammalian red blood cells: too much or too little?. Nat Med 9, 481–482 (2003). https://doi.org/10.1038/nm0503-481

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