Bradykinin is a mediator of
brain edema acting through B2 receptors. However, it is not known if
bradykinin mediates the formation of cytotoxic or vasogenic
brain swelling. To investigate this question we subjected rats to a cryogenic brain lesion over the left parietal cortex, a model well known to produce predominantly
vasogenic brain edema. We inhibited
bradykinin B2 receptors with the recently characterized nonpeptide B2 receptor antagonist,
LF 16-0687. The animals were assigned to three groups (n = 10, each) receiving 10, or 100 microg/kg/min
LF 16-0687 or vehicle (
0.9% NaCl). Treatment started 15 min before
trauma and was continued for 24 h. Another three groups of animals (n = 10, each) received 10 microg/kg/min
LF 16-0687 starting 30 or 60 min after
trauma or vehicle (
0.9% NaCl) for 24 h. Animals were then sacrificed and swelling and water content of the brain were determined. In the vehicle treated group the traumatized hemisphere swelled by 9.3 +/- 1.1% as compared to the untraumatized contralateral side. Pretreatment with 10 microg/kg/min
LF 16-0687 decreased
brain swelling significantly to 6.4 +/- 1.3% (p < 0.05). Pre-treatment with 100 microg/kg/min was found to be less effective and did not result in a significant reduction of
brain swelling (7.4 + 1.3%). Treatment with
LF 16-0687 for 24 h (10 microg/kg/min) started 30 or 60 min after
trauma did not reduce brain water content or hemispheric swelling. These results demonstrate that
brain injury-mediated
bradykinin production induces
vasogenic brain edema by B2 receptor stimulation. Our findings further clarify the role of
bradykinin in the pathophysiology of
brain edema formation and confirm the therapeutic potency of
bradykinin B2 receptor inhibition.