What is the Efficiency of ATP Signaling from Erythrocytes to Regulate Distribution of O2 Supply Within the Microvasculature?

Abstract

Erythrocytes appear to be ideal sensors for regulating microvascular O(2) supply as they release the potent vasodilator ATP in an O(2) saturation-dependent manner. Whether erythrocytes play a significant role in regulating O(2) supply in the complex environment of diffusional O(2) exchange among capillaries, arterioles, and venules, depends on the efficiency with which erythrocytes signal the vascular endothelium. If one assumes that the distribution of purinergic receptors is uniform throughout the microvasculature, then the most efficient site for signaling should occur in capillaries, where the erythrocyte membrane is in close proximity to the endothelium. ATP released from erythrocytes would diffuse a short distance to P(2y) receptors inducing an increase in blood flow, possibly the result of endothelial hyperpolarization. We hypothesize that this hyperpolarization varies across the capillary bed depending upon erythrocyte supply rate and the flux of O(2) from these erythrocytes to support O(2) metabolism. This would suggest that the capillary bed would be the most effective site for erythrocytes to communicate tissue oxygen needs. Electrically coupled endothelial cells conduct the integrated signal upstream where arterioles adjust vascular resistance, thus enabling ATP released from erythrocytes to regulate the magnitude and distribution of O(2) supply to individual capillary networks.