The red blood cell as an oxygen sensor: what is the evidence?

The matching of oxygen supply with demand requires the existence of a mechanism within the tissue capable of both sensing tissue oxygen need and inducing alterations in vascular perfusion necessary to meet that need. Historically, localized sites within the tissue and the vessels themselves have been investigated with the sensor site failing to be determined. Within the last decade, studies have focused on the red blood cell, the efficient carrier of oxygen, as a possible candidate. The red blood cell is clearly capable of sensing oxygen levels, as its extent of haemoglobin desaturation (decrease in oxygen content) is intimately tied with tissue oxygen demand. In addition, numerous studies have indicated that the red blood cell is capable of releasing increased amounts of adenosine 5'-triphosphate (ATP) as oxygen content falls and its haemoglobin becomes desaturated. Within the vasculature, intraluminal ATP has been shown to induce a vasodilator response which is conducted along the vessels resulting in augmentation of tissue perfusion. While details of the red blood cell's role are still under investigation, evidence presented here supports the intriguing idea that the mobile red blood cell may itself be able to augment blood flow and oxygen delivery wherever and whenever the need might arise. Such a mechanism eliminates the requirement for a diverse network of sensing sites throughout the vasculature and should provide a more efficient means of appropriately matching oxygen supply with demand.