title: Effects of selective and non-selective endothelin antagonists on ischemia-reperfusion damage in the isolated perfused murine liver.
abstract: The objective of the present study was to clarify the differential effects of endothelinA (ETA) and ETB antagonism in the early phase of ischemia-reperfusion damage. Male Sprague Dawley rats were randomly divided into 4 groups: control (n = 10), bosentan (40 nM; n = 10), BQ-485 (20 nM; n = 10), and BQ-788 (50 nM; n = 10) to compare the effects of ETA or ETB or both ETA and ETB antagonists against the warm ischemia-reperfusion damage of murine livers. Isolated livers were perfused with oxygenated Krebs-Henseleit bicarbonate buffer solution and ET antagonists for 30 min before inducing warm ischemia (non-recirculating system). After 40 min without perfusate, measurements (portal pressure, O2 tensions of influent and effluent perfusate, liver enzymes, etc.) were taken up to 60 min after reperfusion. The BQ-788 group had significantly more liver damage than did the other groups, and more O2 consumption than did the bosentan group. BQ-485 and bosentan were more protective at some points after reperfusion. Antagonism of only the ETB receptors is detrimental, but antagonism of the ETA receptors appears to have a role in protecting the liver from warm ischemia-reperfusion damage in the early phase.
authors.affiliation: Department of Anesthesiology, National Defense Medical College, Saitama, Japan. biosmith@mxc.meshnet.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Higuchi
authors.forename: F
authors.initials: F
authors.lastname: Karasawa
authors.forename: T
authors.initials: T
authors.lastname: Sato
mesh_terms: D000410:Alanine Transaminase / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D007770:L-Lactate Dehydrogenase / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010101:Oxygen Consumption; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001381:Azepines; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010880:Piperidines; D013449:Sulfonamides; C083116:BQ 485; C086539:BQ 788; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077300:Bosentan