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 endothelin(A) (ETA) and ETB antagonism in the early phase of ischemia-re perfusion damage. Male Sprague Dawley rats were randomly divided into 4 gro ups: control (n = 10), bosentan (40 nhl; n=10), BQ-485 (20 nM; n=10), and B Q-788 (50 nM; n=10) to compare the effects of ETA or ETB or both ETA and ET B 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 ischemi a (non-recirculating system). After 40 min without perfusate, measurements (portal pressure, O-2 tensions of influent and effluent perfusate, liver en zymes, etc.) were taken up to 60 min after reperfusion. The BQ-788 group had significantly more liver damage than did the other gro ups, and more O-2 consumption than did the bosentan group. BQ-485 and bosen tan were more protective at some points after reperfusion. Antagonism of on ly the ETB receptors is detrimental, but antagonism of the ETA receptors ap pears to have a role in protecting the liver from warm ischemia-reperfusion damage in the early phase.