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Reversal of the vasoconstrictor step of hyperacute xenogeneic rejection of the liver by endothelin antagonists
Author(s) -
Zhang Baimeng,
Wen Lanling,
Gomola Alexandra,
Massault PierrePhilippe,
Cherruau Brigitte,
Houssin Didier,
Weill Bernard,
Calmus Yvon
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703295
Subject(s) - bosentan , endothelin receptor , perfusion , endothelin 1 , vasoconstrictor agents , antagonist , endothelins , in vivo , endothelin receptor antagonist , medicine , vasoconstriction , endocrinology , pharmacology , chemistry , receptor , biology , microbiology and biotechnology
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 ET A and ET B endothelin receptors, or that of bosentan, a mixed ET A /ET B antagonist, antagonized the vasoconstrictor effect of 10% xenogeneic human serum, as well as that of 10 −9 M 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