Key result
Ang II antagonists protect nonsteatotic liver grafts from reperfusion injury, while Ang 1-7 antagonists protect steatotic grafts.
Why the study?
Numerous steatotic livers are discarded due to poor tolerance of ischemia-reperfusion injury, and the roles of Ang II and Ang-(1-7) in liver graft damage are not fully understood.
Do Ang II receptor antagonists and Ang-(1-7) receptor antagonists protect against hepatic ischemia-reperfusion damage in steatotic and nonsteatotic liver grafts from Zucker rats?
Do Ang II receptor antagonists and Ang-(1-7) receptor antagonists protect against hepatic ischemia-reperfusion damage in steatotic and nonsteatotic liver grafts from Zucker rats?
Angiotensin II receptor antagonists protect nonsteatotic liver grafts, while Angiotensin-(1-7) receptor antagonists specifically protect steatotic liver grafts from ischemia-reperfusion injury.
May suggest steatosis-specific RAS antagonist selection for liver grafts; hypothesis-generating and requires clinical confirmation.
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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Alfany-Fernández et al. (2009) studied Liver transplantation (steatotic and nonsteatotic grafts). Ang-II receptor antagonists and Ang-(1-7) receptor antagonists was evaluated on Hepatic ischemia-reperfusion damage associated with transplantation. Ang II receptor antagonists protected nonsteatotic liver grafts against ischemia-reperfusion damage, whereas Ang-(1-7) receptor antagonists were effective only in steatotic grafts.
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