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+)](i)) 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.
Kapela
Adam
A
Department of Biomedical Engineering, Florida International University, Miami, Florida, USA.
Bezerianos
Anastasios
A
Tsoukias
Nikolaos M
NM
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D004594:Electrophysiology; D042783:Endothelial Cells; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008564:Membrane Potentials; D008962:Models, Theoretical; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D013152:Splanchnic Circulation / Q000502:physiology*
D009569:Nitric Oxide; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D009638:Norepinephrine