A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity

作者：Kapela Adam; Nagaraja Sridevi; Tsoukias Nikolaos M^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2010, 298(1): H52-H65.

DOI：10.1152/ajpheart.00546.2009

• intercellular communication
• membrane potential
• calcium dynamics

Kapela A, Nagaraja S, Tsoukias NM. A mathematical model of vasoreactivity in rat mesenteric arterioles. II. Conducted vasoreactivity. Am J Physiol Heart Circ Physiol 298: H52-H65, 2010. First published October 23, 2009; doi:10.1152/ajpheart.00546.2009.-This study presents a multicellular computational model of a rat mesenteric arteriole to investigate the signal transduction mechanisms involved in the generation of conducted vasoreactivity. The model comprises detailed descriptions of endothelial (ECs) and smooth muscle (SM) cells (SMCs), coupled by nonselective gap junctions. With strong myoendothelial coupling, local agonist stimulation of the EC or SM layer causes local changes in membrane potential (V(m)) that are conducted electrotonically, primarily through the endothelium. When myoendothelial coupling is weak, signals initiated in the SM conduct poorly, but the sensitivity of the SMCs to current injection and agonist stimulation increases. Thus physiological transmembrane currents can induce different levels of local Vm change, depending on cell's gap junction connectivity. The physiological relevance of current and voltage clamp stimulations in intact vessels is discussed. Focal agonist stimulation of the endothelium reduces cytosolic calcium (intracellular Ca(2+) concentration) in the prestimulated SM layer. This SMC Ca(2+) reduction is attributed to a spread of EC hyperpolarization via gap junctions. Inositol (1,4,5)-trisphosphate, but not Ca(2+), diffusion through homocellular gap junctions can increase intracellular Ca(2+) concentration in neighboring ECs. The small endothelial Ca(2+) spread can amplify the total current generated at the local site by the ECs and through the nitric oxide pathway, by the SMCs, and thus reduces the number of stimulated cells required to induce distant responses. The distance of the electrotonic and Ca(2+) spread depends on the magnitude of SM prestimulation and the number of SM layers. Model results are consistent with experimental data for vasoreactivity in rat mesenteric resistance arteries.

• 出版日期2010-1