Plasma contains a pool of nitrite that is produced in large part when nitric oxide reacts with oxygen. At reduced oxygen pressures when hemoglobin in the erythrocyte is partially deoxygenated, we have shown that nitrite reacts with the deoxygenated hemoglobin chains. This reaction reduces nitrite to NO providing a source af NO under the hypoxic conditions where it is needed to facilitate the flow of blood through the microcirculation. We have shown that the nitric oxide bioactivity is maintained by an intermediate formed during this reaction. The release of this bioactivity to the vasculature is facilitated by the binding of deoxygenated hemoglobin to the membrane and the coupled release of this NO as well as nitrite, while it is bound to the membrane. Chemical, as well as animal and human studies are being performed to determine the physiological role of erythrocyte delivery of NO to the vasculature.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000433-05
Application #
8552411
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$618,067
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Rifkind, Joseph M; Salgado, Maria T; Cao, Zeling (2012) Regulation of oxygen delivery by the reaction of nitrite with RBCs under hypoxic conditions. Adv Exp Med Biol 737:183-9
Salgado, Maria T; Ramasamy, Somasundaram; Tsuneshige, Antonio et al. (2011) A new paramagnetic intermediate formed during the reaction of nitrite with deoxyhemoglobin. J Am Chem Soc 133:13010-22
Rifkind, Joseph M; Nagababu, Enika; Ramasamy, Somasundaram (2011) The quaternary hemoglobin conformation regulates the formation of the nitrite-induced bioactive intermediate and the dissociation of nitric oxide from this intermediate. Nitric Oxide 24:102-9
Nagababu, Enika; Rifkind, Joseph M (2011) Routes for Formation of S-Nitrosothiols in Blood. Cell Biochem Biophys :
Nagababu, Enika; Rifkind, Joseph M (2011) Determination of s-nitrosothiols in biological fluids by chemiluminescence. Methods Mol Biol 704:27-37
Salgado, Maria T; Nagababu, Enika; Rifkind, Joseph M (2009) Quantification of intermediates formed during the reduction of nitrite by deoxyhemoglobin. J Biol Chem 284:12710-8
Rifkind, Joseph M; Nagababu, Enika; Cao, Zeling et al. (2009) Nitrite-induced improved blood circulation associated with an increase in a pool of RBC-NO with no bioactivity. Adv Exp Med Biol 645:27-34
Cao, Zeling; Bell, Jeffrey B; Mohanty, Joy G et al. (2009) Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite-induced vasodilation. Am J Physiol Heart Circ Physiol 297:H1494-503