Bradykinin mediates acute
inflammation by increasing microvascular permeability, vasodilation, leukocyte migration and accumulation, and the production of
arachidonic acid via
phospholipase A2 activation.
Arachidonic acid metabolites, or
eicosanoids, are potent modulators of
biological functions, particularly
inflammation.
Bradykinin exerts its inflammatory effects via the
bradykinin B2 receptor. The aim of this study was to evaluate the effect of a
bradykinin B2 receptor antagonist,
FR173657 (FR), on 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 II 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 (pHi), SMA blood flow, and mucosal tissue blood flow were measured during the reperfusion period. The serum
thromboxane B2 and 6-keto-prostaglandin F1alpha 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 II in comparison with Group I. Histopathological examination showed less severe mucosal damage after reperfusion in Group II than in Group I. The serum
thromboxane B2 and 6-keto-prostagland in F1alpha levels were significantly lower in Group II 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.