Electrical Propagation of Vasodilatory Signals in Capillary Networks
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Electrical Propagation of Vasodilatory Signals in Capillary Networks Pilhwa Lee1 Received: 12 November 2019 / Accepted: 9 September 2020 / Published online: 23 September 2020 © Society for Mathematical Biology 2020
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. Keywords Vasodilation · Calcium-activated potassium channel · Purinergic signal · ATP hypothesis
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Pilhwa Lee [email protected] Molecular and Integrative Physiology, University of Michigan, Ann Arbor, USA
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1 Introduction We investigate the influence of vasodilatory signals in the electrical propagation in the endothelium of microvasculature and dilation in the upstream arterioles. Blood flow regulation in the microcirculation is crucial for maintaining relevant pressure tone and tissue oxygenation. In arterioles and capillary microvasculature, the downstream signaling of oxygen demand or hypertension induces upstream conducted vasodilation (Bagher and Segal 2011). The upstream propagation of electrical signals in the microvasculature is activated by exercise at a healthy state (Duncker and Bache 2008). However, it may cause dysfunction at disease states such as diabetes (Fitzgerald et al. 2005; Park et al. 2008; Bender et al. 2009), obesity (Haddock et al. 2011), and hypertension (Brahler et al. 2009). Microvascular dilation is regulated by agonists such as cholinergic acetylcholine (ACh) (Doyle and Duling 1997), plasma ATP (Ellsworth 2000), and also via sympathetic control of β-adre
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