[Studies on the involvement of bradykinin in the formation of ischemic brain edema].

Bradykinin (BK) is known to be involved in the inflammatory process causing various tissue reactions such as peripheral vasodilation and increased vascular permeability. The aims of this study was to investigate the involvement of the kallikrein-kinin system (K-K system) in the generation and progression of cerebral edema following an ischemic incident. First, after infusion of BK into the internal carotid artery, the cerebral water content was measured and electron microscopic observations were made to investigate changes of permeability using the horseradish peroxidase (HRP) tracer method. Secondly, the plasma and tissue BK levels, cerebral water content and energy metabolites (ATP, lactate and pyruvate) were measured at scheduled intervals. This was achieved using the cerebral ischemia model induced in spontaneously hypertensive rats (SHR) in which the common carotid artery were occluded (BLCO) with clips in both sides. The plasma and tissue BK were measured by radioimmunoassay. Furthermore, aprotinin and soybean trypsin inhibitor (SBTI), which specifically inhibit the K-K system, were applied to the same model and the effects on cerebral edema and metabolism were tested. At three hours after infusion of BK, cerebral edema was observed on the infused hemisphere and an increase of pinocytosis in the vessels was observed in the electron microscopic study. The chronological observation of cerebral water content revealed that it started to increase after BLCO, reaching a peak level at 30 min after reperfusion, before decreasing slightly. The plasma BK levels also showed an increase at the end of BLCO and reached a peak level at 30 min after reperfusion, decreasing thereafter. The tissue BK levels elevated significantly at 30 min after reperfusion and returned to control levels at 60 min. The ATP levels decreased remarkably after BLCO, and then increased after 30 min of reperfusion. The lactate levels increased during ischemia and became higher at 30 min after reperfusion and then decreased. The pyruvate levels did not change during this time period. In the treated group, aprotinin showed significantly lower levels of cerebral water content compared to the control. This group also showed lower lactate accumulation and preservation of ATP levels than the control. SBTI also had significantly lower water content than the control, but there was no difference in the metabolites. These results showed that BK augments the progression of brain edema and that the BK level corresponded with progression of ischemic brain edema and the suppression of BK decreased edema formation. These novel findings indicate a close relationship between BK and ischemic brain edema.