The non‐neuronal cholinergic system: sources of vascular ACh

Abstract

The localisation of muscarinic receptors in vascular endothelial cells and the consequences of activation of these receptors are extensively documented. However, it is not known if endogenous acetylcholine is available to activate receptors, and if so where it originates. As acetylcholine (ACh), its receptors and synthesising enzymes are widely expressed in extra‐neuronal cells and tissues (the non‐neuronal cholinergic system) including blood cells, we investigated a potential role for these cells as a source of endogenous ACh to stimulate the endothelium. Isolated rat mesenteric arteries were cut open and fixed en‐face. Endothelial cells were loaded with a calcium dye to measure levels of intracellular calcium using confocal microscopy. Endothelial cells exhibited transient but pronounced calcium increases when exposed to rat whole blood. The frequency of endothelial cell calcium events, average fluorescence and the number of active cells increased significantly above the spontaneous basal activity. ATP was shown not to be a component of this response, however, a trend in sensitivity to block with atropine (1μM) was observed. Taken together these data suggest that ACh may originate in sufficient quantities from blood cells to stimulate endothelial cell calcium increases. As such this may represent a significant auto or paracrine influence on vascular tone.Work funded by the British Heart Foundation.