Erythrocyte-derived ATP and perfusion distribution: role of intracellular and intercellular communication

In complex organisms, both intracellular and intercellular communication are critical for the appropriate regulation of the distribution of perfusion to assure optimal O(2) delivery and organ function. The mobile erythrocyte is in a unique position in the circulation as it both senses and responds to a reduction in O(2) tension in its environment. When erythrocytes enter a region of the microcirculation in which O(2) tension is reduced, they release both O(2) and the vasodilator, ATP, via activation of a specific and dedicated signaling pathway that requires increases in cAMP, which are regulated by PDE3B. The ATP released initiates a conducted vasodilation that results in alterations in the distribution of perfusion to meet the tissue's metabolic needs. This delivery mechanism is modulated by both positive and negative feedback regulators. Importantly, defects in low O(2) -induced ATP release from erythrocytes have been observed in several human disease states in which impaired vascular function is present. Understanding of the role of erythrocytes in controlling perfusion distribution and the signaling pathways that are responsible for ATP release from these cells makes the erythrocyte a novel therapeutic target for the development of new approaches for the treatment of vascular dysfunction.