Abstract
The effects of different doses of angiotensin II (0.02 to 0.5 microgram kg-1 min-1 on mean arterial blood pressure, tissue blood flow and tissue vascular resistance were investigated in BD9 rats. Blood flow was measured using the uptake of 125I- or 14C-labelled iodoantipyrine (125I-IAP and 14C-IAP). Spatial heterogeneity of blood flow within tumours, before and after angiotensin II infusion, was also measured using 14C-IAP and an autoradiographic procedure. Mean arterial blood pressure rose steeply with angiotensin II dose. Blood flow to skeletal muscle, skin overlying the tumour, contralateral skin, small intestine and kidney tended to decline in a dose-dependent manner. Blood flow to the tumour was also reduced (to 80% of control values) but there was no dose response. Blood flow to the heart was slightly increased and blood flow to the brain was unaffected by angiotensin II. Vascular resistance, in all tissues, was increased by angiotensin II infusion. The increase in tumour tissue was similar to that found in skeletal muscle and small intestine and is likely to be caused by a direct vasoconstricting effect of the drug rather than autoregulation of tumour blood flow in the face of an increase in perfusion pressure. The reduction in overall blood flow at the highest perfusion pressure was due to a preferential effect of angiotensin II at the tumour periphery. These results show that some tumours, at least, can respond directly to the effects of vasoactive agents.
Highlights
Selective manipulation of tumour blood flow using vasoactive agents is potentially useful for some forms of therapy
In the present study absolute blood flow to tumours and normal tissues was measured in order to calculate tissue vascular resistance and determine whether angiotensin II has any direct vasoconstricting effects on the blood vessels supplying the tumour
A dose response for angiotensin II was obtained in order to investigate whether there is an optimum dose at which the effects of an increase in perfusion pressure outweigh any vasoconstrictior, lntra-tumour heterogeneity of blood flow has important implications for therapy
Summary
One of the aims of the present study was to determine the reactivity of tumour blood vessels to a particular vasoactive agent, angiotensin II. The aims of this study were (1) to determine a dose response for the effects of angiotensin II on tumour and normal tissue blood flow (2) to investigate the mechanisms of these effects by measuring perfusion pressure and calculating
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