INTRACAROTID HISTAMINE INFUSION INCREASES BLOOD TUMOR PERMEABILITY INRG2 GLIOMA

Histamine will alter blood flow and permeability in systemic and cereb ral vessels. We reported that intracarotid infusion of histamine selec tively increased the blood flow in experimental brain tumours and caus ed extravassation of Evans blue within tumours. In this study, the eff ects of histamine on tumour and brain capillary permeability were quan tified using autoradiography. RG2 glioma cells were implanted in femal e Wistar rats. Seven days after implantation, either low doses of hist amine (1 or 10 mu g kg(-1) min(-1)) or saline as a control was infused through the carotid artery of rats. Regional permeability was measure d by autoradiography using [C-14] aminoisobutyric acid, and the unidir ectional transfer constant, Ki (mu l g(-1) min(-1)), was calculated. I ntracarotid infusion of 10 mu g kg(-1) min(-1) histamine resulted in s ignificant increase in brain tumour permeability, compared to controls . The permeability, Ki, for the 10 mu g kg(-1) min(-1) histamine group , the 1 mu g kg(-1) min(-1) histamine group, and the control group was 18.8 +/- 4.6 (p < 0.05), 14.9 +/- 5.2, 13.9 +/- 3.7 mu l g(-1) min(-1 ), respectively There was no significant change in blood brain permeab ility in other brain regions. The effect of increased permeability by 10 mu g kg(-1) min(-1) histamine was suppressed by the H2-blocker, cim etidine. This suggests that the effect of histamine on tumour capillar ies is mediated by H2-receptors. Intracarotid histamine infusion selec tively increases permeability in brain tumours.