Basic and therapeutic relevance of endothelin-mediated regulation.

摘要: Three endothelin family peptides (endothelin-1, -2 and -3) exert an extremely potent long-lasting vasoconstrictor action as well other various actions through stimulating two subtypes of receptor (ETA ETB). Vascular endothelial cells produce only endothelin-1. Although the pharmacological exogenous endothelin-1 have been extensively analyzed, physiological roles endogenous long obscure. Using selective antagonists, has demonstrated to contribute slightly maintenance regional vascular tone. In gene-targeted mice, their receptors shown play important role in embryonic development neural crest-derived tissues. addition its action, direct mitogenic on cardiovascular tissues, co-mitogenic with a wide variety growth factors vasoactive substances. Endothelin-1 also promotes synthesis secretion substances including extracellular constituents. These effects would appear be naturally concerned and/or aggravation chronic diseases, e.g. hypertension, pulmonary remodeling (restenosis, atherosclerosis), renal failure, heart failure. A great many non-peptide orally active antagonists developed, excellent therapeutic animal models human patients these diseases.