title: The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis.
abstract: Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, mainly secreted by endothelial cells. It acts through two types of receptors: ETA and ETB. Apart from a vasoconstrictive action, ET-1 causes fibrosis of the vascular cells and stimulates production of reactive oxygen species. It is claimed that ET-1 induces proinflammatory mechanisms, increasing superoxide anion production and cytokine secretion. A recent study has shown that ET-1 is involved in the activation of transcription factors such as NF-κB and expression of proinflammatory cytokines including TNF-α, IL-1, and IL-6. It has been also indicated that during endotoxaemia, the plasma level of ET-1 is increased in various animal species. Some authors indicate a clear correlation between endothelin plasma level and morbidity/mortality rate in septic patients. These pathological effects of ET-1 may be abrogated at least partly by endothelin receptor blockade. ET-1 receptor antagonists may be useful for prevention of various vascular diseases. This review summarises the current knowledge regarding endothelin receptor antagonists and the role of ET-1 in sepsis and inflammation.
authors.affiliation: Chair of Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland, akkowalczyk@o2.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Kowalczyk
authors.forename: Paulina
authors.initials: P
authors.lastname: Kleniewska
authors.forename: Michal
authors.initials: M
authors.lastname: Kolodziejczyk
authors.forename: Beata
authors.initials: B
authors.lastname: Skibska
authors.forename: Anna
authors.initials: A
authors.lastname: Goraca
mesh_terms: D000818:Animals; D000077300:Bosentan; D016207:Cytokines / Q000378:metabolism; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction; D013449:Sulfonamides / Q000737:chemistry; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D016207:Cytokines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011725:Pyridines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D013777:Tetrazoles; D013481:Superoxides; C086539:BQ 788; C120582:tezosentan; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)