The key signaling pathways suspected to be activated in vascular endothelial cells (VEC) and smooth muscle cells (VSMC) by the apelin receptor. Apelin binding can promote Gαi, Gαq, and β-arrestin recruitment to the receptor. In the presence of the endothelium, both Gαi and Gαq promote relaxation of smooth muscle cells through nitric oxide and prostacyclin release. In the absence of the endothelium, apelin binds directly to the receptor on the smooth muscle cells and leads to constriction through undetermined intermediate steps but most likely involving PKC, phosphoinositide 3-kinase (PI3K) and myosin light chain phosphorylation. Figure constructed using Servier Medical Art.