endothelín

Endothelin is a potent vasoconstrictor peptide that plays a crucial role in the regulation of vascular tone and blood pressure. It was first identified in 1988 and is primarily produced by the endothelial cells lining the blood vessels. Endothelin exists in three isoforms: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3), with ET-1 being the most abundant and well-studied.

The synthesis of endothelin involves a series of steps starting from preproendothelin, which is cleaved to form big endothelin. This intermediate is then processed by endothelin-converting enzyme (ECE) to produce the active endothelin peptide. Endothelin exerts its effects by binding to two types of receptors: endothelin A (ETA) and endothelin B (ETB) receptors. ETA receptors are primarily found on smooth muscle cells and mediate vasoconstriction, while ETB receptors are located on endothelial cells and are involved in vasodilation through the release of nitric oxide and prostacyclin.

Endothelin is involved in various physiological processes, including the regulation of blood pressure, inflammation, and cell proliferation. However, its overproduction or dysregulation has been implicated in several pathological conditions, such as hypertension, pulmonary arterial hypertension, atherosclerosis, and heart failure. Additionally, endothelin has been shown to play a role in the progression of certain cancers and fibrotic diseases.

The clinical significance of endothelin has led to the development of endothelin receptor antagonists (ERAs), which are used in the treatment of conditions like pulmonary arterial hypertension. These medications block the binding of endothelin to its receptors, thereby reducing vasoconstriction and improving symptoms. Ongoing research continues to explore the potential therapeutic applications of targeting the endothelin system in various diseases.