Intracarotid histamine infusion increases blood tumour permeability in RG2 glioma

Histamine will alter blood flow and permeability in systemic and cerebral vessels. We reported that intracarotid infusion of histamine selectively increased the blood flow in experimental brain tumours and caused extravassation of Evans blue within tumours. In this study, the effects of histamine on tumour and brain capillary permeability were quantified using autoradiography. RG2 glioma cells were implanted in female Wistar rats. Seven days after implantation, either low doses of histamine (1 or 10 micrograms kg-1 min-1) or saline as a control was infused through the carotid artery of rats. Regional permeability was measured by autoradiography using [14C] aminoisobutyric acid, and the unidirectional transfer constant, Ki (microliters g-1 min-1), was calculated. Intracarotid infusion of 10 micrograms kg-1 min-1 histamine resulted in significant increase in brain tumour permeability, compared to controls. The permeability, Ki, for the 10 micrograms kg-1 min-1 histamine group, the 1 micrograms 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 microliters g-1 min-1, respectively. There was no significant change in blood brain permeability in other brain regions. The effect of increased permeability by 10 micrograms kg-1 min-1 histamine was suppressed by the H2-blocker, cimetidine. This suggests that the effect of histamine on tumour capillaries is mediated by H2-receptors. Intracarotid histamine infusion selectively increases permeability in brain tumours.