Reversal of the vasoconstrictor step of hyperacute xenogeneic rejection of the liver by endothelin antagonists

Article date: May 2000

By: Baimeng Zhang, Lanling Wen, Alexandra Gomola, Pierre‐Philippe Massault, Brigitte Cherruau, Didier Houssin, Bernard Weill, Yvon Calmus in Volume 130, Issue 2, pages 402-408

The role of endothelin in the initial vasoconstrictor step of hyperacute xenogeneic rejection was investigated.

Isolated rat livers were perfused in recirculation. Perfusion with human sera provided an ex vivo model of hyperacute rejection in a discordant combination.

Perfusion of 10% xenogeneic serum induced a marked (70%) and sustained reduction of the liver flow and induced the release of endothelin into the perfusion medium. In contrast, perfusion of 10% allogeneic serum or of 10% decomplemented human serum induced a weak (25%) and transient reduction of the liver flow and induced the release of minimal amounts of endothelin. The simultaneous administration of BQ 123 and BQ 788, the respective antagonists of ETA and ETB endothelin receptors, or that of bosentan, a mixed ETA/ETB antagonist, antagonized the vasoconstrictor effect of 10% xenogeneic human serum, as well as that of 10−9M endothelin‐1.

The vasoconstrictor effects of xenogeneic serum on liver circulation are, at least partly, mediated through the release of endothelin by the graft.

The role of endothelin in the initial vasoconstrictor step of hyperacute xenogeneic rejection was investigated.

Isolated rat livers were perfused in recirculation. Perfusion with human sera provided an ex vivo model of hyperacute rejection in a discordant combination.

Perfusion of 10% xenogeneic serum induced a marked (70%) and sustained reduction of the liver flow and induced the release of endothelin into the perfusion medium. In contrast, perfusion of 10% allogeneic serum or of 10% decomplemented human serum induced a weak (25%) and transient reduction of the liver flow and induced the release of minimal amounts of endothelin. The simultaneous administration of BQ 123 and BQ 788, the respective antagonists of ETA and ETB endothelin receptors, or that of bosentan, a mixed ETA/ETB antagonist, antagonized the vasoconstrictor effect of 10% xenogeneic human serum, as well as that of 10−9M endothelin‐1.

The vasoconstrictor effects of xenogeneic serum on liver circulation are, at least partly, mediated through the release of endothelin by the graft.

British Journal of Pharmacology (2000) 130, 402–408; doi:10.1038/sj.bjp.0703295

DOI: 10.1038/sj.bjp.0703295

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