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 angiotensin II (AT II) administration whereby the rate of the continuous AT II infusion was chosen to increase the mean arterial blood pressure (MABP) by 50-70 mmHg. In subcutaneous DS-sarcomas the red blood cell (RBC) flux was assessed using the laser Doppler technique and the mean tumour oxygen partial pressure (pO2) was measured polarographically using O2-sensitive catheter and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact of AT II on tumour pO2 was also mainly tumour volume-related. In small tumours oxygenation decreased with increasing MABP during AT II infusion, whereas in large tumours a positive relationship between blood pressure and O2 status was found. This disparate behaviour might be the result of the co-existence of two functionally distinct populations of tumour vessels. In small tumours, perfusion decreases presumably due to vasoconstriction of pre-existing host vessels feeding the tumour. In larger malignancies, newly formed tumour vessels predominate and seem not to have this vasoresponsive capability (lack of smooth muscle cells and/or AT receptors), resulting in an improvement of perfusion which is not tumour-related per se, but is due to the increased perfusion pressure.
Thews
O
O
Institute of Physiology and Pathophysiology, University of Mainz, Germany.
Kelleher
D K
DK
Vaupel
P
P
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D017078:Laser-Doppler Flowmetry; D008297:Male; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010100:Oxygen