Attenuated erythrocytic ATP release is caused by extracellular hemoglobin.

Abstract

Local regulation of microvascular flow is a complex process evolved to match oxygen supply to the metabolic demands of the tissue. The RBC has been proposed as an O2 sensor through a direct link between the desaturation of intracellular hemoglobin (Hb) and ATP release, leading to vasodilation1. This theory suggests a link between alterations of O2 transport parameters in the plasma space and vasoactivity. Based on theoretical calculations of O2 extraction from RBCs in the presence of Hb‐based oxygen carriers (HBOCs), we hypothesized that that the addition of cell‐free Hb to the extracellular space provides a supplementary O2 source that reduces RBC desaturation and ATP release. In this study, the total O2 concentration of RBC/HBOC suspensions was lowered by additions of deoxygenated saline, and then assayed for ATP production via the luciferin‐luciferase bioluminescence assay. When an acellular Hb cross‐linked between α subunits (αα Hb, p50 = 33 mmHg) was added to the red cell suspension, ATP production was significantly less in the absence of HBOC. These results provide a possible mechanism for HBOC‐induced vasoactivity through delayed release of red cell ATP.1 Ellsworth, ML (2000) Acta Physiol Scand 168: 551‐559.