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Electrical Propagation of Vasodilatory Signals in Capillary Networks

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Abstract

We have developed a computational model to study electrical propagation of vasodilatory signals and arteriolar regulation of blood flow depending on the oxygen tension and agonist distribution in the 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. We have estimated the oxygen saturation parameters in terms of erythrocyte ATP release from the data of a left anterior descending coronary blood perfusion of dog. Regarding 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, a local infusion of acetylcholine induces enhanced electrical propagation that corresponds to physiological relevance. Integrating the electrophysiology of endothelial tube and the electrophysiology/mechanics of a lumped arteriole, we show mechanistically that endothelial purinergic oxygen sensing of ATP released from erythrocytes and local infusion of acetylcholine are 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.

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Acknowledgements

The author acknowledges valuable discussions with Ranjan Pradhan, Brian E. Carlson, and Daniel A. Beard. Especially the formulation of the open probability in \(\hbox {SK}_{\mathrm{Ca}}\) and \(\hbox {IK}_{\mathrm{Ca}}\) channels with NS309 is accredited to Ranjan Pradhan. The author also thanks Steven Segal and Erik Behringer for the experimental data and helpful discussion. This research was partially supported by U01 HL118738-01A1 and NIGMS-P50GM094503.

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  1. Molecular and Integrative Physiology, University of Michigan, Ann Arbor, USA

    Pilhwa Lee

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Correspondence to Pilhwa Lee.

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Lee, P. Electrical Propagation of Vasodilatory Signals in Capillary Networks. Bull Math Biol 82, 128 (2020). https://doi.org/10.1007/s11538-020-00806-y

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