Bradykinin B2 receptor antagonist FR173657 ameliorates small bowel ischemia-reperfusion injury in dogs

Bradykinin mediates acute inflammation by increasing microvascular permeability, vasodilation, leukocyte migration and accumulation, and the production of arachidonic acid via phospholipase A(2) activation. Arachidonic acid metabolites, or eicosanoids, are potent modulators of biological functions, particularly inflammation. Bradykinin exerts its inflammatory effects via the bradykinin B-2) receptor. The aim of this study was to evaluate the effect of a bradykinin B-2 receptor antagonist, FR173657 (FR), oil intestinal ischemia-reperfusion (I/R) injury. Twenty-eight mongrel dogs were divided into four groups (n = 7 per group). Group I underwent I/R alone, Group 11 underwent I/R and received FR treatment, Group III was sham operated, and Group IV was sham operated and received FR treatment. The FR treatment consisted of FR continuously from 30 min prior to ischemia to 2 hr after reperfusion. In the I/R procedure, the superior mesenteric artery (SMA) and vein were clamped for 2 hr and then released to permit reperfusion for 12 hr. The intramucosal pH (pH(i)), SMA blood flow, and mucosal tissue blood flow were measured during the repel-fusion period. The serum thromboxane B-2 and 6-keto-prostaglandin F-1alpha, levels were determined, and tissue samples were examined histologically. Results showed that tissue blood flow, pHi, and SMA blood flow after reperfusion were maintained in Group It in comparison with Group I. Histopathological examination showed less severe mucosal damage after reperfusion in Group 11 than in Group I. The serum thromboxane B-2 and 6-keto-prostagland in F-1alpha, levels were significantly lower in Group 11 than in Group I (P < 0.05). We conclude that FR treatment appears to have clear protective effects on small bowel I/R injury by inhibiting the release of eicosanoids.