Cyclic GMP-specific Phosphodiesterase Inhibition and Intracarotid Bradykinin Infusion Enhances Permeability into Brain Tumors

摘要: Abstract Intracarotid infusion of bradykinin selectively increases the delivery compounds into brain tumors. This study sought to determine role cyclic GMP in increased permeability across blood-tumor barrier (BTB) after bradykinin. In studies, 186 Wistar rats with RG2 gliomas and C6 were used. Transport BTB was quantified by autoradiography reported as a unidirectional transport, Ki, for [14C]dextran (Mr 70,000) [14C]aminoisobutyric acid 103,000), or without inhibition GMP-specific phosphodiesterase soluble guanylate cyclase. We also determined levels tumors normal brain, intracarotid infusion, using RIA. both tracers. Simultaneous inhibitor, zaprinast (20 mg/kg), resulted significantly BTB, compared alone. Zaprinast prolonged effects Pretreatment i.v. cyclase LY-83583 (125 µg/kg), attenuated effect opening BTB. Cyclic (2.8- 2.2-fold, respectively). not infusion. These results show that increasing tumor microvessels can increase response