Reduction of adhesion formation by an angiotensin type 1 receptor antagonist.
OBJECTIVE
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.
Tokinaga
Yasuyuki
Y
Department of Surgical Operating Center, Wakayama Medical University, Wakayama, Japan.
Kimoto
Yoshiki
Y
Ogawa
Koji
K
Mizumoto
Kazuhiro
K
Tange
Kazuaki
K
Hatano
Yoshio
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D000267:Tissue Adhesions / Q000473:pathology* / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013777:Tetrazoles; C081643:candesartan