The effect of systemic arterial hypertension on blood-to-tissue transport in experimental gliomas

Systemic arterial hypertension was induced with epinephrine in 15 rats with 39 transplanted RG-2 brain tumors in an attempt to increase blood-to-tissue transport of a water-soluble compound. In 4 rats, hypertension was induced acutely (< 5 sec), and in 11 hypertension was induced more slowly (over 5 min). Regional values of the unidirectional blood-to-tissue transfer constant (K) of alpha aminoisobutyric acid were measured with quantitative autoradiography. Mean arterial blood pressure (BP) over the experimental period increased from 117 ± 17 mmHg (SD) to 168 ± 18 mmHg in the rats with slowly induced hypertension, and from 124 ± 4 to 142 ± 5 mmHg in the acute hypertension group. Peak BP was 208 ± 16 in the first group and 216 ± 13 mmHg in the second. Intracerebral hemorrhage occurred in 10/15 animals, and there was disruption of BBB in tumor-free brain in 10/15 animals. Averaged mean whole tumor K of AIB in all hypertensive rats was 0.052 ± 0.022 ml/g/min, compared to 0.037 ± 0.015 ml/g/min in normotensive controls; there was no difference in mean tumor K between the two hypertensive groups. However, in intraparenchymal tumors without hemorrhage, K was only 0.039 ± 0.013 ml/g/min. Although the mean K of AIB was higher in brain tumors of the hypertensive rats, the increase is unlikely to be meaningful in terms of augmented delivery of watersoluble drugs to brain tumors, and the high incidence of intracerebral hemorrhage countermands any clinical use of this approach.