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Physiology 22: 97-112, 2007; doi:10.1152/physiol.00042.2006
1548-9213/07 $8.00
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Physiology, Vol. 22, No. 2, 97-112, April 2007
© 2007 Int. Union Physiol. Sci./Am. Physiol. Soc.

REVIEW

Transport and Peripheral Bioactivities of Nitrogen Oxides Carried by Red Blood Cell Hemoglobin: Role in Oxygen Delivery

Pierre Sonveaux1, Irina I. Lobysheva1, Olivier Feron1 and Timothy J. McMahon2

1 Université Catholique de Louvain (UCL), Unit of Pharmacology & Therapeutics, Brussels, Belgium; and
2 Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina mcmah003{at}mc.duke.edu

The biology of NO (nitric oxide) is poorly explained by the activity of the free radical NO (·NO) itself. Although ·NO acts in an autocrine and paracrine manner, it is also in chemical equilibrium with other NO species that constitute stable stores of NO bioactivity. Among these species, S-nitrosylated hemoglobin (S-nitrosohemoglobin; SNO-Hb) is an evolved transducer of NO bioactivity that acts in a responsive and exquisitely regulated manner to control cardiopulmonary and vascular homeostasis. In SNO-Hb, O2 sensing is dynamically coupled to formation and release of vasodilating SNOs, endowing the red blood cell (RBC) with the capacity to regulate its own principal function, O2 delivery, via regulation of blood flow. Analogous, physiological actions of RBC SNO-Hb also contribute to central nervous responses to blood hypoxia, the uptake of O2 from the lung to blood, and baroreceptor-mediated control of the systemic flow of blood. Dysregulation of the formation, export, or actions of RBC-derived SNOs has been implicated in human diseases including sepsis, sickle cell anemia, pulmonary arterial hypertension, and diabetes mellitus. Delivery of SNOs by the RBC can be harnessed for therapeutic gain, and early results support the logic of this approach in the treatment of diseases as varied as cancer and neonatal pulmonary hypertension.

Disclosures: T. J. McMahon has received research funding from Nitrox (a company developing NO-related therapeutics).




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