Abstract
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.
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