Are angiotensin II receptor antagonists useful strategies in steatotic and nonsteatotic livers in conditions of partial hepatectomy under ischemia-reperfusion?

Fernando S. Ramalho, Izabel Alfany-Fernandez, Araní Casillas-Ramirez, Marta Massip-Salcedo, Anna Serafín, Antoni Rimola, Vicente Arroyo, Juan Rodés, Joan Roselló-Catafau, Carmen Peralta

    Research output: Contribution to journalArticleResearchpeer-review

    35 Citations (Scopus)

    Abstract

    We examined whether angiotensin (Ang) II receptor antagonists could be considered a therapeutic strategy in steatotic and non- steatotic livers in conditions of partial hepatectomy under isch- emia-reperfusion (I/R), which is commonly applied in clinical practice to reduce blood loss. We report that Ang II type I receptor (AT1R) antagonist, but not Ang II type II receptor (AT2R) antagonist, increased regeneration in nonsteatotic livers. In the presence of steatosis, both AT1R and AT2R antagonists increased liver regeneration. This effect was stronger when the two were combined. Neither of the Ang II receptor antagonists protected non- steatotic livers against damage. Only the ATlR antagonist, through nitric oxide inhibition, reduced damage in steatotic livers. The combination of the AT1R and AT2R antagonists in steatotic livers conferred a similar degree of protection to AT1R antagonist alone. Herein, we show that p38 mitogen-activated protein kinase (p38) was a key mechanism in the regeneration induced by the Ang II receptor antagonists in both liver types because when this signaling pathway was inhibited, the beneficial effects of the Ang II receptor antagonists on liver regeneration disappeared, regardless of hepatocyte growth factor or transforming growth factor β-hepatic levels. In conclusion, in conditions of partial hepatec- tomy under I/R, the AT1R antagonist for nonsteatotic livers and the AT1R and AT2R antagonists for steatotic livers improved regeneration in the remnant liver through p38 activation. In addition, the combination of the AT1R and AT2R antagonists in stea- totic livers led to stronger liver regeneration than either antagonists used separately and also provided the same protection against damage as that afforded by AT1R antagonist alone. © 2009 by The American Society for Pharmacology and Experimental Therapeutics.
    Original languageEnglish
    Pages (from-to)130-140
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume329
    Issue number1
    DOIs
    Publication statusPublished - 1 Apr 2009

    Fingerprint Dive into the research topics of 'Are angiotensin II receptor antagonists useful strategies in steatotic and nonsteatotic livers in conditions of partial hepatectomy under ischemia-reperfusion?'. Together they form a unique fingerprint.

  • Cite this

    Ramalho, F. S., Alfany-Fernandez, I., Casillas-Ramirez, A., Massip-Salcedo, M., Serafín, A., Rimola, A., Arroyo, V., Rodés, J., Roselló-Catafau, J., & Peralta, C. (2009). Are angiotensin II receptor antagonists useful strategies in steatotic and nonsteatotic livers in conditions of partial hepatectomy under ischemia-reperfusion? Journal of Pharmacology and Experimental Therapeutics, 329(1), 130-140. https://doi.org/10.1124/jpet.108.147835