Losartan supports liver regrowth via distinct boost of portal vein pressure in rodents with 90 % portal branch ligation

Dig Dis Sci. 2013 Aug;58(8):2205-11. doi: 10.1007/s10620-013-2664-3. Epub 2013 Apr 30.

Abstract

Objectives: The study used a model of 90 % portal branch ligation (PBL) in rats to study the effect of losartan on portal vein pressure (PVP) and liver regeneration in rats after PBL.

Methods: A total of 144 male Sprague-Dawley rats were arbitrarily designated into three treatment method groups: a sham operation group (Sham), a PBL treatment group (PBL), and a PBL plus losartan treatment group (PBL + L). Losartan (2 mg/day) was intragastrically gavaged 3 days before the PBL or sham operation to time points of study.

Results: Both the PBL and PBL + L groups showed an intense surge in PVP after PBL treatment, peaking at 12 h postsurgery, then lessening progressively afterwards. PVP was substantially greater in these two groups compared with the Sham group at 6-72 h postsurgery (p < 0.01). Compared with the PBL group, the PBL + L group showed a noticeable reduction in PVP 6-48 h postsurgery (p < 0.05); the PBL group showed considerably raised levels of plasma ALT and AST 6-72 h postsurgery (p < 0.01). Compared to the PBL group, the PBL + L group showed drastically reduced plasma ALT and AST levels 12-72 h postsurgery (p < 0.05).

Conclusions: Losartan supports liver regeneration in 90 % of rats that underwent PBL. The mechanism may be related to losartan's ability to regulate PVP and increase serum hepatocyte growth factor levels.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Gene Expression Regulation / drug effects
  • Ligation
  • Liver / blood supply
  • Liver / pathology
  • Liver Regeneration / drug effects*
  • Losartan / therapeutic use*
  • Male
  • Portal Vein / drug effects*
  • Portal Vein / physiology
  • Portal Vein / surgery
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Proliferating Cell Nuclear Antigen
  • Losartan