Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2015 May 19;112(20):6254-5.
doi: 10.1073/pnas.1506523112. Epub 2015 May 5.

Regulation of oxygen delivery to the body via hypoxic vasodilation

Shathiyah Kulandavelu  1 , Wayne Balkan  1 , Joshua M Hare  2
Affiliations
Comment

Regulation of oxygen delivery to the body via hypoxic vasodilation

Shathiyah Kulandavelu et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: J.M.H. discloses a relationship with Vestion that includes equity, board membership, and consulting.

Figures

Fig. 1.
Fig. 1.
Three proposed mechanisms underlying hypoxic vasodilation. ATP release: Activation of Gi results in increased adenylyl cyclase activity, resulting in increased cAMP followed downstream by increased ATP release. ATP binds to endothelial purinergic receptors on endothelial cells and activates eNOS to stimulate NO-dependent vasodilation. Nitrite reduction: Nitrite entering RBCs reacts with both oxyHb (forming nitrate and metHb) and deoxyHb (forming NO and metHb). The reaction with deoxyHb is favored at low oxygen saturation. Formation of dinitrogen trioxide (N2O3) allows for NO-bioactivity to escape the RBC and mediate vasodilation. SNO-hemoglobin pathway: Hemoglobin becomes S-nitrosylated on a specific and conserved cysteine residue on the β-chain (β93Cys) as RBCs get oxygenated in the lungs. In the R-state, the SNO-Hb remains relatively stable. Upon deoxygenation, SNO-Hb reacts with RBC thiols, such as GSH and anion exchanger-1, to transmit a vasodilatory signal out of the RBC leading to vasodilation. AE-1, anion exchanger-1; ATP, Adenosine triphosphate; cAMP, Cyclic adenosine monophosphate; CFTR, Cystic fibrosis transmembrane regulator; eNOS, endothelial nitric oxide synthase; GSH, glutathione; GSNO, S-nitrosoglutathione; NO, nitric oxide; NO2−, nitrite; NO3−, nitrate; N2O3, dinitrogen trioxide; P2Y, purinergic receptors; PKA, Protein Kinase A.
See this image and copyright information in PMC

Comment on

References

    1. Allen BW, Stamler JS, Piantadosi CA. Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation. Trends Mol Med. 2009;15(10):452–460. - PMC - PubMed
    1. Singel DJ, Stamler JS. Chemical physiology of blood flow regulation by red blood cells: The role of nitric oxide and S-nitrosohemoglobin. Annu Rev Physiol. 2005;67:99–145. - PubMed
    1. Jensen FB. The dual roles of red blood cells in tissue oxygen delivery: Oxygen carriers and regulators of local blood flow. J Exp Biol. 2009;212(Pt 21):3387–3393. - PubMed
    1. González-Alonso J, Olsen DB, Saltin B. Erythrocyte and the regulation of human skeletal muscle blood flow and oxygen delivery: Role of circulating ATP. Circ Res. 2002;91(11):1046–1055. - PubMed
    1. Farias M, 3rd, Gorman MW, Savage MV, Feigl EO. Plasma ATP during exercise: Possible role in regulation of coronary blood flow. Am J Physiol Heart Circ Physiol. 2005;288(4):H1586–H1590. - PubMed

Publication types

LinkOut - more resources