Bradykinin Selectively Opens Blood-Tumor Barrier in Experimental Brain Tumors

Abstract

Bradykinin, infused in low doses (10 μg/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 increased by intracarotid bradykinin infusion. Tracers used to examined permeability included radiolabeled α-aminoisobutyric acid (AIB; MW 103), sucrose (MW 342.3), inulin (MW 5000), and dextran (MW 70,000), horseradish peroxidase (HRP) and Evans blue (EB). Permeability was expressed as the unidirectional transfer constant Ki (μl/g/min). The permeabilities (Ki) of tumors in the bradykinin group versus the control saline 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 < 0.01), 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). Permeabi...