Red blood cell regulation of microvascular tone through adenosine triphosphate

The matching of blood flow with metabolic need requires a mechanism for sensing the needs of the tissue and communicating that need to the arterioles, the ultimate controllers of tissue perfusion. Despite significant strides in our understanding of blood flow regulation, the identity of the O₂ sensor has remained elusive. Recently, the red blood cell, the Hb- containing O₂ carrier, has been implicated as a potential O₂ sensor and contributor to this vascular control by virtue of its concomitant carriage of millimolar amounts of ATP, which it is able to release when exposed to a low- O₂ environment. To evaluate this possibility, we exposed perfused cerebral arterioles to low extraluminal O₂ in the absence and presence of red blood cells or 6% dextran and determined both vessel diameter and ATP in the vessel effluent. Only when the vessels were perfused with red blood cells did the vessels dilate in response to low extraluminal O₂. In addition, this response was accompanied by a significant increase in vessel effluent ATP. These findings support the hypothesis that the red blood cell itself serves a role in determining O₂ supply to tissue.