Angiotensin-converting enzyme inhibitor enalapril reduces formation of hypertrophic scars in a rabbit ear wounding model

Plast Reconstr Surg. 2013 Sep;132(3):361e-371e. doi: 10.1097/PRS.0b013e31829acf0a.


Background: Angiotensin-converting enzyme inhibitors are widely used in medicine because of their antihypertensive and antifibrogenic effects. Angiotensin-converting enzyme activates angiotensin I to angiotensin II, which plays an important regulatory role in wound healing and collagen production. The authors investigated whether systemic administration of angiotensin-converting enzyme inhibitors has any effect on formation of hypertrophic scars using the rabbit ear wound model.

Methods: Sixteen New Zealand albino rabbits were divided into four groups, and four punch defects were created on each ear. The first group received oral enalapril immediately after the creation of punch defects. The second group received oral enalapril on day 28 after the formation of scars. The third group received intralesional steroid injections on days 28 and 35. The fourth group was the control group. The rabbits were killed on day 40. The harvested specimens were analyzed histomorphometrically and immunohistochemically.

Results: Early enalapril application decreased the scar elevation index and fibroblast and capillary counts significantly, compared with the values in the control group. Late enalapril application decreased fibroblast counts significantly; however, there was no difference in scar elevation index compared with the control group. There was no difference between early enalapril application and steroid therapy in terms of scar elevation index and capillary and fibroblast counts. However, early and late enalapril groups displayed lower collagen type III immunoreactivity compared with the steroid and control groups.

Conclusion: Early application of enalapril following dermal injury reduces formation of hypertrophic scars, probably because of its down-regulatory effects on type III collagen production.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Oral
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Cicatrix, Hypertrophic / etiology
  • Cicatrix, Hypertrophic / pathology
  • Cicatrix, Hypertrophic / prevention & control*
  • Drug Administration Schedule
  • Ear, External / injuries*
  • Enalapril / therapeutic use*
  • Female
  • Rabbits
  • Treatment Outcome
  • Triamcinolone Acetonide / therapeutic use
  • Wound Healing
  • Wounds, Penetrating / complications*


  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents
  • Enalapril
  • Triamcinolone Acetonide