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

Microcirculation. 2009 Nov;16(8):694-713. doi: 10.3109/10739680903177539.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / physiology*
  • Calcium / metabolism
  • Calcium Signaling
  • Electrophysiology
  • Endothelial Cells
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Membrane Potentials*
  • Models, Theoretical*
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / physiology
  • Nitric Oxide / metabolism
  • Norepinephrine
  • Paracrine Communication / physiology*
  • Rats
  • Splanchnic Circulation / physiology*


  • Nitric Oxide
  • Inositol 1,4,5-Trisphosphate
  • Calcium
  • Norepinephrine