The hemoglobin-nitric oxide axis: implications for transfusion therapeutics

SUMMARY Understanding mechanisms that regulate nitric oxide (NO) function in the vascular compartment is critical in the context of transfusion-based therapeutics. The role of hemoglobin (Hb), either cell-free or encapsulated within the erythrocyte, has received much attention owing largely to the rapid rate of reactions between NO and either oxy- or deoxyheme. In this review, we discuss the different mechanisms proposed by which NO reactions with Hb are controlled under physiological conditions and which involve both preventing NO-scavenging by Hb and erythrocyte (and Hb)-dependent stimulation of NO-signaling. How these mechanisms may be utilized therapeutically in the design and application of Hb-based oxygen carrier therapeutics is also discussed.