Journal
PEPTIDES
Volume 111, Issue -, Pages 77-88Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2018.10.002
Keywords
Endothelin; Heart failure; Cardiac hypertrophy; Pulmonary hypertension; Receptor antagonist
Funding
- University of Tsukuba Project Research
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Endothelin-1 (ET-1), a 21-amino acid peptide, was initially identified in 1988 as a potent vasoconstrictor and pressor substance isolated from the culture supernatant of porcine aortic endothelial cells. From human genomic DNA analysis, two other family peptides, ET-2 and ET-3, were found. They showed different effects and distribution, suggesting that each peptide may play separate roles in different organs. In the heart, ET-1 also causes positive inotropic and chronotropic responses and hypertrophic activity of the cardiomyocytes. ETs act via activation of two receptor subtypes, ETA and ETB receptors, both of which are coupled to various GTP-binding proteins depending on cell types. Endogenous ET-1 may be involved in progression of various cardiovascular diseases. ET antagonists are currently used clinically in the treatment for patients with pulmonary hypertension, and are considered to have further target diseases as heart failure, cardiac hypertrophy and other cardiac diseases, renal diseases, systemic hypertension, and cerebral vasospasm.
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