Endothelin (ET) is the most potent vasoconstrictor identified so far in vivo, and three isoforms consisting of 21 amino acids, ET-1, ET-2 and ET-3, and the recently discovered ET-4 consisting of 31 amino acids, have been identified, and its receptors are divided into three isoforms, ETA, ETB, ETC, and AngII/ET-1 receptors, in addition to several translocases and multiple intracellular The receptors are divided into ETA, ETB and ETC subtypes and AngII/ET-1 receptors, in addition to several translocases and several intracellular signaling pathways. ET receptor antagonists have been used in the treatment of heart failure and pulmonary hypertension, mainly acting selectively or non-selectively on ETA receptors, but some recent clinical studies on ET receptor antagonists for heart failure have shown disappointing results and have raised awareness of ETB receptor function. ETB receptors are divided into two subtypes, ETB1, which are located in vascular endothelial cells (VEC), and ETB2, which are located in vascular smooth muscle cells (VSMC), and both consist of seven transmembrane lamellar structures that belong to the G protein-coupled receptor superfamily. Sequence integrity. the main difference between ETA and ETB receptor primary structure is at the N-terminal (extracellular membrane part), e.g. the human liver ETB receptor N-terminal is proline-rich, probably related to ligand selectivity. the ETB receptor is inactivated by phosphorylation, which is rapid and therefore short-lived. In the lung, ETB receptors are distributed in alveolar epithelial cells and pulmonary microvasculature. In animal models of hypoxia or pulmonary hypertension, upregulation of ETB2 receptors in VSMC cells and downregulation of ETB1 receptors in VEC cells were observed in the pulmonary arteries. ETB2 receptor upregulation may be related to vascular remodeling due to pathological damage. Alveolar epithelial cells and pulmonary microvasculature are dominated by ETB1 receptors, which are mainly involved in the clearance of ET from the circulation and the reuptake of ET-1 by endothelial cells. For example, intravenous injection of radiolabeled ET-1 and administration of the selective ETB receptor antagonist BQ-788 inhibits its aggregation in the lung and kidney, thus slowing ET-1 clearance in the circulation, whereas selective ETA receptor antagonists do not. ETB receptor deletion leads to increased plasma ET-1, and this response occurs despite increased ETA receptor protein expression, indicating the importance of ETB is important as an ET clearance receptor.