Bradykinin antagonists reduce leukocyte-endothelium interactions after global cerebral ischemia

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B(1) and B(2) receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B(1)/B(2) receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 +/- 20, 6 +/- 8, 9 +/- 10, and 13 +/- 10) and adherent leukocytes (9 +/- 7, 3 +/- 4, 1 +/- 1, and 2 +/- 3. 100 microm(-1) x min(-1) in controls and in animals treated with B(1), B(2), and B(1)/B(2) antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 +/- 11 before and 27 +/- 8 microm 40 minutes after ischemia) in animals treated with the B(2) antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B(1) and the B(1)/B(2) antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.