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 Ca 2+ dynamics and membrane electrophysiology in arteriolar smooth muscle (SMC) and endothelial (EC) cells. Cells are coupled through the exchange of Ca 2+ , Cl − , K + , and Na + ions, inositol 1,4,5‐triphosphate (IP 3 ), and the paracrine diffusion of nitric oxide (NO). EC stimulation reduces intracellular Ca 2+ ([Ca 2+ 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 SK Ca and IK Ca channels. During NE stimulation, IP 3 diffusing from the SMC induces EC Ca 2+ release, which, in turn, moderates SMC depolarization and [Ca 2+ ] i elevation. On the contrary, SMC [Ca 2+ ] i was not affected by EC‐derived IP 3 . Myoendothelial Ca 2+ fluxes had no effect in either cell. The EC exerts a stabilizing effect on calcium‐induced calcium release‐dependent SMC Ca 2+ 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.