TY - GEN
T1 - Nitrite-induced improved blood circulation associated with an increase in a pool of RBC-NO with NO bioactivity
AU - Rifkind, Joseph M.
AU - Nagababu, Enika
AU - Cao, Zeling
AU - Barbiro-Michaely, Efrat
AU - Mayevsky, Avraham
PY - 2009
Y1 - 2009
N2 - The reduction of nitrite by RBCs producing NO can play a role in regulating vascular tone. This hypothesis was investigated in rats by measuring the effect of nitrite infusion on mean arterial blood pressure (MAP), cerebral blood flow (CBF) and cerebrovascular resistance (CVR) in conjunction with the accumulation of RBC-NO. The nitrite infusion reversed the increase in MAP and decrease in CBF produced by L-NAME inhibition of e-NOS. At the same time there was a dramatic increase in RBC-NO. Correlations of RBC-NO for individual rats support a role for the regulation of vascular tone by this pool of NO. Furthermore, data obtained prior to treatment with L-NAME or nitrite are consistent with a contribution of RBC reduced nitrite in regulating vascular tone even under normal conditions. The role of the RBC in delivering NO to the vasculature was explained by the accumulation of a pool of bioactive NO in the RBC when nitrite is reduced by deoxygenated hemoglobin chains. A comparison of R and T state hemoglobin demonstrated a potential mechanism for the release of this NO in the T-state present at reduced oxygen pressures when blood enters the microcirculation. Coupled with enhanced hemoglobin binding to the membrane under these conditions the NO can be released to the vasculature.
AB - The reduction of nitrite by RBCs producing NO can play a role in regulating vascular tone. This hypothesis was investigated in rats by measuring the effect of nitrite infusion on mean arterial blood pressure (MAP), cerebral blood flow (CBF) and cerebrovascular resistance (CVR) in conjunction with the accumulation of RBC-NO. The nitrite infusion reversed the increase in MAP and decrease in CBF produced by L-NAME inhibition of e-NOS. At the same time there was a dramatic increase in RBC-NO. Correlations of RBC-NO for individual rats support a role for the regulation of vascular tone by this pool of NO. Furthermore, data obtained prior to treatment with L-NAME or nitrite are consistent with a contribution of RBC reduced nitrite in regulating vascular tone even under normal conditions. The role of the RBC in delivering NO to the vasculature was explained by the accumulation of a pool of bioactive NO in the RBC when nitrite is reduced by deoxygenated hemoglobin chains. A comparison of R and T state hemoglobin demonstrated a potential mechanism for the release of this NO in the T-state present at reduced oxygen pressures when blood enters the microcirculation. Coupled with enhanced hemoglobin binding to the membrane under these conditions the NO can be released to the vasculature.
UR - http://www.scopus.com/inward/record.url?scp=61849120730&partnerID=8YFLogxK
U2 - 10.1007/978-0-387-85998-9_5
DO - 10.1007/978-0-387-85998-9_5
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C2 - 19227446
AN - SCOPUS:61849120730
SN - 9780387859972
T3 - Advances in Experimental Medicine and Biology
SP - 27
EP - 34
BT - Oxygen Transport to Tissue XXX
A2 - Liss, Per
A2 - Hansell, Peter
A2 - Bruley, Duane
A2 - Harrison, David
ER -