Endothelium-dependent vasodilators do not cause propagated intercellular Ca2+ waves in vascular endothelial...

Local application of a number of vasoactive agents affects vasomotor tone not only downstream to the point of application but also upstream. The mechanism(s) of upstream propagation is unknown. In endothelial cell monolayers, mechanical stimulation of one cell leads to intercellular propagation of increases in endothelial cell (EC) [Ca2+]i. In this study, we tested whether increases in EC [Ca2+]i induced by the local application of the endothelium-dependent vasodilators ATP, bradykinin and acetylcholine could spread across the monolayer. We demonstrate that unlike the response seen to a mechanical stimulus, there was no significant propagation of increases in EC [Ca2+]i levels in response to localized application of these agents. These findings suggest that upstream vasodilation in response to endothelium-dependent vasodilators is not mediated by propagation of EC [Ca2+]i waves and suggest that other electrical or chemical signals are responsible.