The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Clin Invest Med. 2015 Aug 9;38(4):E164-72. doi: 10.25011/cim.v38i4.24261.

Abstract

Purpose: Angiotensin converting enzyme inhibitors (ACEI) and type I angiotensin receptor blockers (ARB) have been shown to exert significant effects on bone tissue via a local renin-angiotensin-aldosterone system (RAS). The aim of our study was to delineate their influences on fracture healing process.

Methods: Sixty adult male Wistar Albino rats were divided into three groups. After undergoing surgical femoral fracture and fixation, the ACEI group received 10 mg/kg of Enalapril, the ARB group received 10 mg/kg of Losartan and the Control group did not receive any medication. Fracture healing was evaluated at second and fifth postoperative weeks by the Lane-Sandhu radiological staging system and by histological scoring system of Huoet al. ACE expression in fracture callus was studied by immunohistochemistry.

Results: Both ACEI and ARB groups showed less fibrous tissue in the fracture area at the second week, but the histologic score differences were significant only between Control and ARB groups. At the fifth week, however, both radiological and histological scores for the ACEI group were significantly higher than both ARB and Control groups, while the scores for ARB and Control groups were similar. The presence of ACE expression in fracture callus was also observed.

Conclusion: ACEIs had significant positive effects on fracture repair. Losartan failed to display these stimulatory effects, which suggests that local RAS in bone tissue exerts its actions via alternative receptors or pathways than the AT1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Enalapril / pharmacology*
  • Fracture Healing / drug effects*
  • Losartan / pharmacology*
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Enalapril
  • Losartan