Role of bradykinin B-2 receptors in the formation of vasogenic brain edemain rats

Bradykinin is a mediator of brain edema acting through B-2 receptors. Howev er, it is not known if bradykinin mediates the formation of cytotoxic or va sogenic brain swelling. To investigate this question we subjected rats to a cryogenic brain lesion over the left parietal cortex, a model well known t o produce predominantly vasogenic brain edema. We inhibited bradykinin B-2 receptors with the recently characterized nonpeptide B-2 receptor antagonis t, LF 16-0687. The animals were assigned to three groups (n = 10, each) rec eiving 10, or 100 mug/kg/min LF 16-0687 or vehicle (0.9% NaCl). Treatment s tarted 15 min before trauma and was continued for 24 h. Another three group s of animals (n = 10, each) received 10 mug/kg/min LF 16-0687 starting 30 o r 60 min after trauma or vehicle (0.9% NaCl) for 24 h. Animals were then sa crificed and swelling and water content of the brain were determined. In th e vehicle treated group the traumatized hemisphere swelled by 9.3 1.1% as c ompared to the untraumatized contralateral side. Pretreatment with 10 mug/k g/min LF 160687 decreased brain swelling significantly to 6.4 +/- 1.3% (p < 0.05). Pre-treatment with 100 mug/kg/min was found to be less effective an d did not result in a significant reduction of brain swelling (7.4 +/- 1.3% ). Treatment with LF 16-0687 for 24 h (10 mug/kg/min) started 30 or 60 min after trauma did not reduce brain water content or hemispheric swelling. Th ese results demonstrate that brain injury-mediated bradykinin production in duces vasogenic brain edema by B-2 receptor stimulation. Our findings furth er clarify the role of bradykinin in the pathophysiology of brain edema for mation and confirm the therapeutic potency of bradykinin B-2 receptor inhib ition.