The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow - PubMed

Affiliations

• PMID: 19837879
• DOI: 10.1242/jeb.023697

Review

The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow

Frank B Jensen. J Exp Biol. 2009 Nov.

Abstract

Vertebrate red blood cells (RBCs) seem to serve tissue oxygen delivery in two distinct ways. Firstly, RBCs enable the adequate transport of O(2) between respiratory surfaces and metabolizing tissues by means of their high intracellular concentration of hemoglobin (Hb), appropriate allosteric interactions between Hb ligand-binding sites, and an adjustable intracellular chemical environment that allows fine-tuning of Hb O(2) affinity. Secondly, RBCs may sense tissue O(2) requirements via their degree of deoxygenation when they travel through the microcirculation and release vasodilatory compounds that enhance blood flow in hypoxic tissues. This latter function could be important in matching tissue O(2) delivery with local O(2) demand. Three main mechanisms by which RBCs can regulate their own distribution in the microcirculation have been proposed. These are: (1) deoxygenation-dependent release of ATP from RBCs, which stimulates production of nitric oxide (NO) and other vasodilators in the endothelium; (2) release of vasoactive NO from S-nitroso-Hb upon deoxygenation; and (3) reduction of naturally occurring nitrite to vasoactive NO by deoxygenated Hb. This Commentary inspects all three hypotheses with regard to their mechanisms, experimental evidence in their support and details that remain unresolved. The prime focus is on human/mammalian models, where most evidence for a role of erythrocyte ATP and NO release in blood flow regulation have accumulated. Information from other vertebrate groups is integrated in the analysis and used to discuss the evolutionary origin and general relevance of each hypothesis.

Similar articles

• Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle.

  Premont RT, Reynolds JD, Zhang R, Stamler JS. Premont RT, et al. Circ Res. 2020 Jan 3;126(1):129-158. doi: 10.1161/CIRCRESAHA.119.315626. Epub 2019 Oct 8. Circ Res. 2020. PMID: 31590598 Free PMC article. Review.

• Hypoxic vasodilation by red blood cells: evidence for an s-nitrosothiol-based signal.

  Diesen DL, Hess DT, Stamler JS. Diesen DL, et al. Circ Res. 2008 Aug 29;103(5):545-53. doi: 10.1161/CIRCRESAHA.108.176867. Epub 2008 Jul 24. Circ Res. 2008. PMID: 18658051 Free PMC article.

• Erythrocyte-dependent regulation of human skeletal muscle blood flow: role of varied oxyhemoglobin and exercise on nitrite, S-nitrosohemoglobin, and ATP.

  Dufour SP, Patel RP, Brandon A, Teng X, Pearson J, Barker H, Ali L, Yuen AH, Smolenski RT, González-Alonso J. Dufour SP, et al. Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H1936-46. doi: 10.1152/ajpheart.00389.2010. Epub 2010 Sep 17. Am J Physiol Heart Circ Physiol. 2010. PMID: 20852046 Free PMC article.

• Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport.

  Jensen FB. Jensen FB. Acta Physiol Scand. 2004 Nov;182(3):215-27. doi: 10.1111/j.1365-201X.2004.01361.x. Acta Physiol Scand. 2004. PMID: 15491402 Review.

• Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction.

  Nagababu E, Ramasamy S, Abernethy DR, Rifkind JM. Nagababu E, et al. J Biol Chem. 2003 Nov 21;278(47):46349-56. doi: 10.1074/jbc.M307572200. Epub 2003 Sep 2. J Biol Chem. 2003. PMID: 12952953

Cited by

• The Effect of Molecular Hydrogen on Functional States of Erythrocytes in Rats with Simulated Chronic Heart Failure.

  Deryugina AV, Danilova DA, Pichugin VV, Brichkin YD. Deryugina AV, et al. Life (Basel). 2023 Feb 2;13(2):418. doi: 10.3390/life13020418. Life (Basel). 2023. PMID: 36836774 Free PMC article.

• Rho-kinase inhibition improves haemodynamic responses and circulating ATP during hypoxia and moderate intensity handgrip exercise in healthy older adults.

  Racine ML, Terwoord JD, Ketelhut NB, Bachman NP, Richards JC, Luckasen GJ, Dinenno FA. Racine ML, et al. J Physiol. 2022 Jul;600(14):3265-3285. doi: 10.1113/JP282730. Epub 2022 May 29. J Physiol. 2022. PMID: 35575293 Free PMC article. Clinical Trial.

• Nitric oxide synthetic pathway in red blood cells is impaired in coronary artery disease.

  Eligini S, Porro B, Lualdi A, Squellerio I, Veglia F, Chiorino E, Crisci M, Garlaschè A, Giovannardi M, Werba JP, Tremoli E, Cavalca V. Eligini S, et al. PLoS One. 2013 Aug 5;8(8):e66945. doi: 10.1371/journal.pone.0066945. Print 2013. PLoS One. 2013. PMID: 23940508 Free PMC article.

• Comparison of human erythrocyte purine nucleotide metabolism and blood purine and pyrimidine degradation product concentrations before and after acute exercise in trained and sedentary subjects.

  Dudzinska W, Suska M, Lubkowska A, Jakubowska K, Olszewska M, Safranow K, Chlubek D. Dudzinska W, et al. J Physiol Sci. 2018 May;68(3):293-305. doi: 10.1007/s12576-017-0536-x. Epub 2017 Apr 21. J Physiol Sci. 2018. PMID: 28432611 Free PMC article.

• Genetic variants of endothelial PAS domain protein 1 are associated with susceptibility to acute mountain sickness in individuals unaccustomed to high altitude: A nested case-control study.

  Guo LI, Zhang J, Jin J, Gao X, Yu J, Geng Q, Li H, Huang L. Guo LI, et al. Exp Ther Med. 2015 Sep;10(3):907-914. doi: 10.3892/etm.2015.2611. Epub 2015 Jul 1. Exp Ther Med. 2015. PMID: 26622413 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems