Reduction of adhesion formation by an angiotensin type 1 receptor antagonist

Langenbecks Arch Surg. 2011 Jan;396(1):127-32. doi: 10.1007/s00423-010-0665-7. Epub 2010 Jul 1.

Abstract

Purpose: Adhesion formations are important causes of intestinal obstruction and can lead to infertility in women. The formation of adhesion appears to be determined by the fibrinolytic activity. Fibrinolysis itself is controlled by the plasminogen activator system, and several studies have shown that angiotensin type 1 (AT(1)) receptor antagonists can reduce plasminogen activator inhibitor-1 (PAI-1) expression, but the effect of AT(1) receptor antagonists on PAI-1 expression involved in the adhesion formation remains unclear. The aim of this study was to investigate whether an AT(1) antagonist, candesartan, can reduce PAI-1 mRNA expression using experimental model of peritoneal adhesions, which seems to reflect post-operative adhesions.

Methods: Using the experimental bowel adhesion rat model, we compared adhesion formation evaluated by the adhesion scoring system and PAI-1 mRNA expression.

Results: The adhesion score and PAI-1 mRNA expression were significantly increased in the experimental bowel adhesion rat model. Candesartan administration decreased adhesion score and abolished increase in PAI-1 mRNA expression.

Conclusions: The AT(1) receptor antagonist, candesartan, significantly decreased the severity of intraperitoneal adhesion, which was associated with an inhibition of PAI-1 mRNA expression in the mesenterium of rats. It suggests that AT(1) receptor antagonists may be useful for the prevention of adhesion formation after surgery.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Benzimidazoles / pharmacology*
  • Disease Models, Animal*
  • Gene Expression / drug effects
  • Male
  • Plasminogen Activator Inhibitor 1 / analysis*
  • Plasminogen Activator Inhibitor 1 / genetics
  • RNA, Messenger / genetics
  • Rats
  • Tetrazoles / pharmacology*
  • Tissue Adhesions / pathology*
  • Tissue Adhesions / prevention & control*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Tetrazoles
  • candesartan