Endotheline

Endothelines are primarily formed by vascular endothelia. They are involved in complex regulatory mechanisms in various organs and exert a number of pharmacological effects.

• Depending on the receptor addressed, endothelin-1:
  • Vasoconstriction (ETA) or dilatation (ETB)
  • Hypertrophy/Fibrosis (ETA, heart)
  • Fibrosis/apoptosis/hypertrophy (ETB, heart)
  • Aldosterone release (ETB).

The main formation sites for endothelin-1 are the endothelial cells of the lung, but also epithelial cells, macrophages, granulocytes, macrophages, fibroblasts and osteoblasts. The release of ET-1 is regulated at the gene level. It is induced by thrombin, angiotensin II, adrenalin, cortisol, endotoxin, hypoxia, growth factors of T cells and macrophages.

Involvement of endothelin-1 in pathophysiology is considered likely in acute renal failure, Raynaud's phenomenon, bronchial asthma, primary pulmonary hypertension and progressive systemic scleroderma.

Acute effects of the peptide ET-1 are, besides strong vasoconstriction, platelet aggregation, fibrosis, vascular hypertrophy and inflammatory reactions. It can activate fibroblasts and macrophages and induce proliferation and procollagen synthesis in fibroblasts in addition to chemotaxis. The proliferation of endothelium, fibroblasts and vascular smooth muscle cells leads to vascular occlusion, necrosis and ulcers. Overexpression of ET-1 plays a crucial role in pulmonary arterial hypertension, collagenosis and pulmonary fibrosis. Elevated ET levels correlate with the severity and course of the disease. Receptors for ET-1 have been abundantly detected in skin and pulmonary vessels.

Endothelin-1 is stimulated by UV-B rays. The peptide is also produced by keratinocytes, among others. It promotes the proliferation, chemotaxis and melanin production of melanocytes. It also plays a decisive role in melanocyte homeostasis and migration (Haass NK et al. 2005).

Bosentan is an endothelin receptor antagonist.

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