Electrical propagation of vasodilatory signals in capillary networks

Abstract

A computational model is developed to study electrical propagation of vasodilatory signals and arteriolar regulation of blood flow depending on the oxygen tension and agonist distribution in capillary network. The involving key parameters of endothelial cell-to-cell electrical conductivity and plasma membrane area per unit volume were calibrated with the experimental data on an isolated endothelial tube of mouse skeletal feeding arteries. The oxygen saturation parameters in terms of ATP release from erythrocytes are estimated from the data of a left anterior descending coronary blood perfusion of dog. In regard to the acetylcholine induced upstream conduction, our model shows that spatially uniform superfusion of acetylcholine attenuates the electrical signal propagation, and blocking calcium activated potassium channels suppresses that attenuation. On the other hand, local infusion of acetylcholine induces enhanced electrical propagation that corresponds to physiological relevance. In the integration of the endothelial tube and the lumped arterioles vessel model, we show that endothelial purinergic oxygen sensing of ATP released from erythrocytes and local infusion of acetylcholine are all individually effective to induce vasodilatory signals to regulate blood flow in arterioles. We have recapitulated the upstream vasomotion in arterioles from the elevated oxygen tension in the downstream capillary domain. This study is a foundation for characterizing effective pharmaceutical strategies for ascending vasodilation and oxygenation.