While agonist-mediated signaling by the endothelium is acknowledged to control virtually all vascular functions, how the endothelium distinguishes low-level concentration fluctuations from noise, and decodes and integrates physiologically relevant information is unclear. Recently we demonstrated that the endothelium decodes agonist signaling by using cells with differing affinities that are organized into spatially-restricted clusters of cells (Wilson, 2016). By utilising cellular hubs to integrate population-wide inputs the endothelium enhances the bandwidth of collective responses (Wilson, 2016). Here we have investigated whether or not different agonists use the same cell hubs to integrate signals or if signals are routed via agonist specific detector cells. In surgically-opened carotid arteries obtained from male (Sprague-Dawley, 150-250g) rats killed by overdose with Pentoject (Schedule 1; Animals (Scientific Procedures) Act 1986), calcium signalling was studied in a large field of endothelium (~150 cells). The muscarinic agonist carbachol and purinergic agonist ATP evoked repeatable, complex calcium signalling across the endothelial field. The calcium signals for each agonist began in discrete clusters of cells and progressed from there as propagating waves of calcium. The number of different clusters of cells activated and the extent of propagation of the calcium wave increased with agonist concentration. With increasing concentration of each agonist, the amplitude of the calcium rise in each activated cell also increased. Carbachol produced a response in 50% of cells (EC50 = 200.5 nM; 95% confidence interval, 113.3-354.9 nM; n = 3) at a lower concentration when compared with ATP (EC50 = 11.68 nM; 95% confidence interval, 9.28-14.69 nM; n = 3). Furthermore, the lowest concentrations of each agonist that produced activity 100% of cells did not elicited maximum calcium rises. High concentrations of ATP (≥ 10 µM) produced an inhibitory effect of endothelial calcium signals. Together, these results suggest the endothelium is organized to function as a collective in detecting and relaying signals. Cells are recruited based on their affinity for the concentration agonist and the endothelium integrates population-wide inputs for efficient high-fidelity signaling. The spatial relationship of various agonist detector cells will be discussed.