Effect of angiotensin II on intermittent tumour blood flow and acute hypoxia in the murine SCCVII carcinoma.
Effects of the vasoconstrictor angiotensin II on tumour microvascular perfusion and oxygenation were examined in the murine SCCVII carcinoma grown subcutaneously in C3H/He mice. Angiotensin II infusion (2 micrograms/kg/min) caused an increase in mouse arterial blood pressure from 85 (2) mm Hg (mean, S.D.) to 112 (7) mm Hg. During drug infusion, tumour red blood cell (RBC) flow (measured by laser doppler flowmetry) increased 206 (50%) (P less than 0.001) in unanaesthetised animals and 305 (90%) (P less than 0.001) in mice immobilised with ketamine and diazepam. As assessed using a fluorescent double-staining technique, angiotensin II reduced staining mismatch (indicative of intermittent blood flow) in SCCVII microvasculature from 8.1 (2.5%) of total vessels to 2.0 (1.3%) (P less than 0.001). However, a large proportion of this reduction could be attributed to volume loading. Angiotensin II reduced but did not completely eliminate the radiobiological acute hypoxia which results from intermittent tumour vessel non-perfusion. We propose that angiotensin II improves tumour microcirculatory flow distribution via its systemic actions, by elevating perfusion pressure, thereby preventing collapse and/or temporary flow stasis in tumour microvessels.
Trotter
M J
MJ
Medical Biophysics Unit, British Columbia Cancer Research Centre, Vancouver, Canada.
Chaplin
D J
DJ
Olive
P L
PL
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000098:blood supply*; D000860:Hypoxia / Q000139:chemically induced; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation
D000804:Angiotensin II