Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation

Perfusion and oxygenation of experimental tumours were studied during angio tensin II (AT II) administration whereby the rate of the continuous AT II i nfusion was chosen to increase the mean arterial blood pressure (MABP) by 5 0-70 mmHg. In subcutaneous DS-sarcomas the red blood cell (RBC) flux was as sessed using the laser Doppler technique and the mean tumour oxygen partial pressure (pO(2)) was measured polarographically using O-2-sensitive cathet er and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small rumours, RBC flux decreased with rising MA BP whereas in larger rumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact o f AT II on tumour pO(2) was also mainly tumour volume-related. In small rum ours oxygenation decreased with increasing MABP during AT II infusion, wher eas in large tumours a positive relationship between blood pressure and O-2 status was found. This disparate behaviour might be the result of the co-e xistence of two functionally distinct populations of tumour vessels. In sma ll tumours, perfusion decreases presumably due to vasoconstriction of pre-e xisting host vessels feeding the tumour. In larger malignancies, newly form ed tumour vessels predominate and seem not to have this vasoresponsive capa bility (jack of smooth muscle cells and/or AT receptors), resulting in an i mprovement of perfusion which is not tumour-related per se, but is due to t he increased perfusion pressure. (C) 2000 Cancer Research Campaign.