BRADYKININ SELECTIVELY OPENS BLOOD-TUMOR BARRIER IN EXPERIMENTAL BRAIN-TUMORS

Bradykinin, infused in low doses (10 mu g/kg/min) through the carotid artery ipsilateral to RG2 glioma in rats, significantly increased the permeability in tumor capillaries to six different tracers of varying molecular weights compared with intracarotid infusion of saline alone. Permeability in normal brain capillaries was not significantly increa sed by intracarotid bradykinin infusion. Tracers used to examined perm eability included radiolabeled cr-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horsera dish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant K-i (mu l/g/min). The permeabi lities (K-i) of tumors in the bradykinin group versus the control sali ne group for AIB, sucrose, inulin, and dextran were 25.91 +/- 6.78 vs. 13.95 +/- 4.29 (p < 0.01), 17.90 +/- 2.65 vs. 10.75 +/- 4.55 (p < 0.0 1), 23.92 +/- 6.99 vs. 6.20 +/- 4.37 (p < 0.01), and 17.84 +/- 1.00 vs . 1.47 +/- 1.24(p < 0.001), respectively (mean +/- SD). Permeability o f RG2 gliomas to high molecular weight dextran (70,000) was 12-fold hi gher in the bradykinin group than in the saline infusion group. Intrac arotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect . The permeability of normal brain capillaries was unaffected by intra carotid bradykinin infusion. The increased permeability was reversed 2 0 min after stopping the intracarotid infusion. Electron microscopic a nd gross qualitative analysis was performed using HRP and EB. Intracar otid bradykinin infusion increased HRP and EB within tumor tissue but not normal tissue. We believe that intracarotid infusion of bradykinin will be a useful technique for selective delivery of antitumor compou nds to brain tumors.