A mathematical model of vasoreactivity in rat mesenteric arterioles: I. Myoendothelial communication

To study the effect of myoendothelial communication on vascular reactivity, we integrated detailed mathematical models of Ca2+ dynamics and membrane electrophysiology in arteriolar smooth muscle (SMC) and endothelial (EC) cells. Cells are coupled through the exchange of Ca2+, Cl−, K+, and Na+ ions, inositol 1,4,5‐triphosphate (IP3), and the paracrine diffusion of nitric oxide (NO). EC stimulation reduces intracellular Ca2+ ([Ca2+ in the SMC by transmitting a hyperpolarizing current carried primarily by K+. The NO‐independent endothelium‐derived hyperpolarization was abolished in a synergistic‐like manner by inhibition of EC SKCa and IKCa channels. During NE stimulation, IP3diffusing from the SMC induces EC Ca2+ release, which, in turn, moderates SMC depolarization and [Ca2+]i elevation. On the contrary, SMC [Ca2+]i was not affected by EC‐derived IP3. Myoendothelial Ca2+ fluxes had no effect in either cell. The EC exerts a stabilizing effect on calcium‐induced calcium release‐dependent SMC Ca2+ oscillations by increasing the norepinephrine concentration window for oscillations. We conclude that a model based on independent data for subcellular components can capture major features of the integrated vessel behavior. This study provides a tissue‐specific approach for analyzing complex signaling mechanisms in the vasculature.

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