Effects of selective and non-selective endothelin antagonists on ischemia-reperfusion damage in the isolated perfused murine liver.
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.
Tanaka
K
K
Department of Anesthesiology, National Defense Medical College, Saitama, Japan. biosmith@mxc.meshnet.or.jp
Higuchi
H
H
Karasawa
F
F
Sato
T
T
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
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