Objective  To study joint effects of bradykinin (BK) and papaverine (PA) on blood-tumor barrier (BTB) permeability and zonula occludens 1 (ZO-1) expression.

  Methods  Glioma model was established in Sprague-Dawley rats. BTB permeability was assessed by Evans blue (EB) extravasation method; the expression of ZO-1 protein and mRNA were determined with immunohistochemistry assay and reverse transcriptase-polymerase chain reaction.

  Results  Significantly increased EB contents (0.487 ± 0.03, 0.503 ± 0.029, and 0.875 ± 0.040 μg/g) were detected in brain tissues of the rats administrated with BK, PA, and BK plus PA compared with that (0.182 ± 0.026 μg/g) in control rats (P < 0.01 for all) and the increase of EB content of the rats treated with BK plus PA was significantly higher than that of the rats treated with only BK or PA (both P < 0.01). The expressions of ZO-1 protein in brain tumor tissues of the rats treated with BK, PA, and BK plus PA were 0.259 ± 0.008, 0.252 ± 0.010, and 0.135 ± 0.015 and all the expressions were significantly decreased in comparison with that (0.379 ± 0.011) of the control rats (all P < 0.01) and the decrease of the rats treated BK plus PA was significantly lower than that of the rats treated with only BK or PA (both P < 0.01); significantly decreased ZO-1 m-RNA expression was also observed in brain tumor tissues of the rats exposed to BK (0.735 ± 0.036), PA (0.695 ± 0.050), and BK plus PA (0.420 ± 0.047) than that (0.876 ± 0.062) of the control group (all P < 0.01) and the decrease in the rats exposed to BK plus PA was significantly lower than that in the rats only exposed to BK or PA (both P < 0.01).

  Conclusion  Administration of BK and PA have synergistic effect on the opening of BTB in rats and the effect may related to down-regulation of ZO-1 expression.