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Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin‐(1–7) in Steatotic Grafts
Author(s) -
AlfanyFernandez I.,
CasillasRamirez A.,
BintanelMorcillo M.,
Brosnihan K. B.,
Ferrario C. M.,
Serafin A.,
Rimola A.,
Rodés J.,
RosellóCatafau J.,
Peralta C.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2008.02521.x
Subject(s) - medicine , angiotensin ii , transplantation , receptor , liver transplantation , renin–angiotensin system , pharmacology , endocrinology , blood pressure
Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia‐reperfusion(I/R). The injurious effects of angiotensin (Ang)‐II and the benefits of Ang‐(1–7) in various pathologies are well documented. We examined the generation of Ang II and Ang‐(1–7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang‐II receptors antagonists and Ang‐(1–7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang‐(1–7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang‐(1–7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang‐(1–7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang‐(1–7), which is specific for steatotic liver grafts.