The endothelium is the single innermost layer of cells in blood vessels and it controls virtually every cardiovascular function including vascular tone, nutrient exchange, blood cell recruitment, blood clotting and the formation of new blood vessels. Dysfunction in the endothelium leads to cardiovascular diseases that include hypertension, heart failure and stroke. However, the underlying dysfunction occurring in the endothelium that leads to cardiovascular disease is largely unknown. In most studies the averaged behavior of thousands of endothelial cells is examined because it is often assumed that the endothelium maximizes the tissues response to perturbations through coordinated responses in a homogeneous population of cells. Our recent data has shown that the endothelium is neither a uniform population of identical cells nor a random distribution of heterogeneous cells but an assembly of heterogeneous cells that are exquisitely organized in a highly refined structure that is essential to function. The endothelium is a web-like network of clusters of agonist sensing cells and linked communicating cells - like a vast switchboard. We have also found the network organization is disrupted in obesity and in hypertension. In this study, advanced single cell recording techniques, will be used to analyze the concurrent dynamic activity from thousands of individual endothelial cells in intact blood vessels. The nature and mechanisms of interactions of several endothelial activators across the network will be examined. The objective is to determine if the impaired function of the endothelium in cardiovascular disease arises from changes in the organization of the network interactions rather than altered performance of individual cells.