The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

As a systemic inflammatory response to infection, sepsis describes a complex clinical syndrome that results in progressively advance stage, probably evoke septic shock, multiple organ dysfunction syndrome and ultimately cause to death. Sepsis is markedly enhanced by proinflammatory cytokines that can trigger a systemic inflammatory cascade mediated by chemokines, vasoactive amines, complement and coagulation system as well as reactive oxygen species (ROS). In 1988, endothelin (ET)-1 was identified as a vasoactive amine from endothelium which has a 21 amino acid peptide. It has been demonstrated with the experimental and clinical studies that endothelin acts as an important role in sepsis and septic shock pathogenesis. Moreover, endothelin receptor antagonists have been studied as novel therapeutic target for treatment of sepsis and septic shock and according to these studies beneficial results have been obtained Mitogen-activated protein kinase signal transduction pathway is stimulated by ET-1 which activates a variety of downstream molecules; it is believed that ET-1could play an important role in the development of sepsis, septic shock, and multiple organ dysfunction syndrome by events that can cause increased reactive oxygen species (ROS) production, inflammation, endothelial dysfunction, abnormal vascular tonus, and vascular remodelling.