[Selective enhancement of tumor blood flow and drug delivery to brain tumors in experimental rat gliomas under angiotensin II-induced hypertension].
Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II)-induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or without AT II-induced hypertension. A suspension of 5 x 10(5)/10 microliters 9L gliosarcoma cells was inoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2 +/- 2.6 ml/100 g/min; mean +/- SEM) and the contralateral caudate-putamen (23.0 +/- 1.8 ml/100g/min) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9 +/- 4.1 ml/100g/min) in the normal rats (p less than 0.01). Intravenous administration of AT II at a dose of 0.4-0.6 microgram/body/min increased the mean arterial blood pressure from 96.5 +/- 4.7 mmHg to 138.0 +/- 3.6 mmHg. AT II-induced hypertension resulted in an approximate 1.8(1.1 - 3.6)-fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hypertension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemotherapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malignant brain tumors.
Ogasawara
H
H
Department of Neurosurgery, Hiroshima University School of Medicine, Japan.
Kiya
K
K
Kurisu
K
K
Hotta
T
T
Mikami
T
T
Sugiyama
K
K
Uozumi
T
T
D000804:Angiotensin II / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D005047:Etoposide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005910:Glioma / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow
D000804:Angiotensin II; D005047:Etoposide