Nitric oxide redox reactions and red cell biology

Three hypotheses explain a role for red blood cells (RBCs) in delivering NO to the vasculature: (a) "the SNOHb hypothesis" involves the uptake of NO by RBCs with NO transferred from the heme to the β-93 thiol in the R quaternary conformation, followed by the release to membrane thiols in the T quaternary conformation; and (b and c) "the nitrite hypotheses" bypass the intrinsic difficulties of transporting the highly reactive NO, by reutilizing the nitrite formed when NO reacts with oxygen. Deoxyhemoglobin reduces this nitrite back to NO. The distinction between the two nitrite mechanisms depends on the importance of intermediate species formed during nitrite reduction. Without bioactive intermediates, the NO must be immediately released to avoid binding to deoxyhemoglobin. The "nitrite intermediate hypothesis" enables the RBCs to store a pool of potentially bioactive NO until it is released from the cell. In this review, we critically compare these different proposals for the transport/delivery of NO by RBCs. We also compare the redox properties in the RBCs associated with NO with the redox properties associated with oxygen.