Haemoglobin Saturation Controls The Red Blood Cell Mediated Hypoxic Vasorelaxation

  • Andrew G. Pinder
  • Stephen C Rogers
  • Keith Morris
  • Philip E. James
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 645)


The vasorelaxant properties of red blood cells (RBCs) have been implicated in both the control of normal vascular tone and the protection of tissues from ischemic events. The identity of the vasorelaxant released from RBCs has yet to be elucidated, however growing evidence suggests that nitric oxide bound to the ß93 cysteine residue of haemoglobin (SNO-Hb) may be responsible. The vasorelaxant moiety is released during the transition of haemoglobin from its R (oxygenated) to T (deoxygenated) state. We subsequently chose to assess the significance of haemoglobin saturation on the capacity of RBCs to mediate hypoxic vasorelaxation.

Human RBC samples suspended in saline were manipulated in a thin film rotating tonometer, designed to rapidly change haemoglobin saturation within the time frame of circulatory transit. Various cycles of oxygenation and deoxygenation were performed. The vasorelaxant properties of the RBCs were analysed using an aortic ring bioactivity assay, wherein changes in isometric tension were recorded to study vessel relaxation. The rabbit aortic rings were preconstricted with phenylephrine under hypoxic conditions (~1% O2) prior to RBC addition.

Highly saturated RBCs (98.22% ± 0.45 HbO2) elicited significantly (P<0.001) more relaxation of hypoxic blood vessels compared to those partially saturated (20.40% ± 5.28 HbO2). Upon re-oxygenation, previously de-oxygenated RBCs were also capable of eliciting vessel relaxation, which was not significantly different from that observed with the original oxygenated RBC relaxation response. Interestingly, the relaxant capability


Nitric Oxide Aortic Ring Extracellular Milieu Average Saturation Haemoglobin Saturation 
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  1. 1.
    C.E. Cooper: Nitric oxide and iron proteins. Biochim Biophys Acta1999, 1411(2-3):290-309.PubMedCrossRefGoogle Scholar
  2. 2.
    A.J .Hobbs, M.T. Gladwin, R.P. Patel, D.L. Williams, A.R. Butler: Haemoglobin: NO transporter, NO inactivator or NOne of the above? Trends Pharmacol Sci2002, 23(9):406-411.PubMedCrossRefGoogle Scholar
  3. 3.
    T.J. McMahon, R.E. Moon, B..P. Luschinger, M.S. Carraway, A.E. Stone, B.W. Stolp, A.J. Gow, J.R.Pawloski, P. Watke, D.J. Singel, et al: Nitric oxide in the human respiratory cycle. Nat Med2002, 8(7):711-717.PubMedGoogle Scholar
  4. 4.
    P.E. James, D. Lang , T. Tufnell-Barret, A.B. Milsom, M.P. Frenneaux: Vasorelaxation by red blood cells and impairment in diabetes: reduced nitric oxide and oxygen delivery by glycated hemoglobin. Circ Res 2004, 94(7):976-983.PubMedCrossRefGoogle Scholar
  5. 5.
    A. Doctor, R. Platt, M.L. Sheram, A. Eischeid, T. McMahon, T. Maxey, J. Doherty, M. Axelrod, J. Kline, M. Gurka et al: Hemoglobin conformation couples erythrocyte S-nitrosothiol content to O2 gradients. Proc Natl Acad Sci USA 2005, 102(16):5709-5714.PubMedCrossRefGoogle Scholar
  6. 6.
    J.S. Stamler, L. Jia, J.P. Eu, T.J. McMahon , I.T. Demchenko, J. Bonaventura , K. Gernert, C.A. Piantadosi: Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science1997, 276(5321):2034-2037.PubMedCrossRefGoogle Scholar
  7. 7.
    M.L. Ellsworth: Red blood cell-derived ATP as a regulator of skeletal muscle perfusion. Med Sci Sports Exerc2004, 36(1):35-41.PubMedCrossRefGoogle Scholar
  8. 8.
    K. Cosby, K.S. Partovi, J.H. Crawford, R.P.Patel, C.D. Reiter, S. Martyr, B.K. Yang, M.A. Waclawiw, G. Zalos, X. Xu et al: Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med2003.Google Scholar
  9. 9.
    J.H. Crawford, T.S. Isbell, Z. Huang, S. Shiva, B.K. Chacko, A.N. Schechter, V.M. Darley-Usmar, J.D. Kerby, J.D. Lang, D. Jr., Kraus et al: Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood2006, 107(2):566-574.PubMedCrossRefGoogle Scholar
  10. 10.
    J.R. Pawloski, D.T. Hess, J.S. Stamler: Export by red blood cells of nitric oxide bioactivity. Nature2001, 409(6820):622-626.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Andrew G. Pinder
    • 1
  • Stephen C Rogers
    • 1
  • Keith Morris
    • 2
  • Philip E. James
    • 1
  1. 1.Department of CardiologyWales Heart Research Institute, School of Medicine, Cardiff UniversityUnited Kingdom
  2. 2.School of Applied SciencesUniversity of Wales Institute CardiffUK

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