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 (less than 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 water-soluble drugs to brain tumors, and the high incidence of intracerebral hemorrhage countermands any clinical use of this approach.