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Effect of angiotensin II and bradykinin inhibition in rat reduced‐size liver transplantation
Author(s) -
PadrissaAltés Susagna,
FrancoGou Rosa,
Boillot Olivier,
Serafín Anna,
Rimola Antoni,
Arroyo Vicente,
Rodés Joan,
Peralta Carmen,
RosellóCatafau Joan
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21693
Subject(s) - medicine , bradykinin , antagonist , angiotensin ii , liver transplantation , receptor antagonist , liver regeneration , receptor , transplantation , pharmacology , endocrinology , reperfusion injury , angiotensin converting enzyme , renin–angiotensin system , ischemia , regeneration (biology) , biology , blood pressure , microbiology and biotechnology
This study examined whether angiotensin II (Ang II) blockers [Ang II type I receptor antagonist, Ang II type II receptor antagonist, and angiotensin converting enzyme (ACE) inhibitor] could reduce hepatic injury and improve regeneration in reduced‐size orthotopic liver transplantation (ROLT) and whether the beneficial effects of ischemic preconditioning (PC) in ROLT could be explained by changes in Ang II. We show that small liver grafts generated Ang II after ROLT and that this was associated with increased angiotensinogen and ACE messenger RNA expression. Furthermore, inhibition of Ang II did not contribute to PC‐induced protection in ROLT. All Ang II blockers reduced hepatic injury, but none of them promoted liver regeneration. Bradykinin (BK) receptor antagonist improved liver regeneration but did not reduce hepatic injury in ROLT. Finally, the combination of Ang II blockers and BK receptor antagonists in ROLT reduced hepatic injury and improved liver regeneration. In conclusion, treatments with either Ang II blockers or BK receptor antagonists cannot, on their own, improve the outcome of ROLT. Although Ang II blockers can reduce hepatic ischemia‐reperfusion injury and BK receptor antagonists can promote liver regeneration, neither confers both benefits at the same time. Consequently, it may be of clinical interest to apply both treatments simultaneously. Liver Transpl 15:313–320, 2009. © 2009 AASLD.