Regulation of Oxygen Delivery by the Reaction of Nitrite with RBCs Under Hypoxic Conditions

  • Joseph M. Rifkind
  • Maria T. Salgado
  • Zeling Cao
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 737)


A number of studies indicate a contribution of red blood cells (RBCs) to nitrite induced vasodilation. These processes are thought to involve nitrite reduction to nitric oxide (NO) by deoxygenated hemoglobin chains. NO generated in the RBC should, however, immediately be scavenged by hemoglobin, apparently negating any possible contribution of this reaction to vasodilation. We have been able to resolve this paradox by showing that nitrite reacted hemoglobin has an unexpectedly high affinity for the red cell membrane. This high affinity contributes to RBC induced vasodilation by two different pathways. (1) The increased membrane binding activates glycolysis and the synthesis of ATP. This newly synthesized ATP is released from the RBC under hypoxic conditions. The released ATP interacts with purinergic receptors on the endothelium that stimulate the synthesis of NO by endothelial NO synthase. This reaction will induce vasodilation without requiring that NO be released from the RBC. (2) The interaction with the membrane, of intermediates formed during the reaction of nitrite with deoxygenated hemoglobin, stimulates the release of NO from these intermediates. NO released on the membrane can escape the large pool of intracellular hemoglobin and be released into the vasculature resulting in vasodilation. Both of these processes linked to membrane associated nitrite reacted hemoglobin explain a role for RBCs in nitrite induced vasodilation.


Nitric Oxide Glycolytic Enzyme Purinergic Receptor Total Heme Nitric Oxide Analyzer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the Intramural Research Program of the NIH, National Institute on Aging.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Joseph M. Rifkind
    • 1
  • Maria T. Salgado
    • 1
  • Zeling Cao
    • 1
  1. 1.The Molecular Dynamics NIA/NIHBaltimoreUSA

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