Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition

Dig Dis Sci. 2007 Apr;52(4):1060-70. doi: 10.1007/s10620-006-9124-2. Epub 2007 Mar 7.


Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor alpha (TNF-alpha). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-alpha expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS)-induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-alpha, Bcl-2, and Bax expression. TNF-alpha mRNA was significantly lower with ACE-I treatment compared to placebo at every time point, as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology*
  • Colitis / physiopathology
  • Colon / blood supply
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Enalaprilat / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Flow Cytometry
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptidyl-Dipeptidase A / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Regional Blood Flow / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Angiotensin-Converting Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Dextran Sulfate
  • Peptidyl-Dipeptidase A
  • Enalaprilat