Spatial heterogeneity of tumour blood flow modification induced by angiotensin II: Relationship to receptor distribution
✍ Scribed by Gillian M. Tozer; Katija M. Shaffi; Vivien E. Prise; Katrina M. Bell
- Book ID
- 102649995
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 730 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Angiotensin II (ATll) has potential for improving delivery of blood-borne anti-cancer agents to tumours by increasing tumour blood flow. However, ATII-induced hypertension is not always accompanied by an increase in tumour blood flow due to significant constriction of the tumour vasculature. Such unpredictability in tumour response to ATll limits the clinical usefulness of this approach. In this study, the potential of assessing numbers of binding sites for ATll as a predictor of tumour blood flow response to intravenous administration of ATll was investigated. The distribution of AT11 receptors in the rat P22 carcinosarcoma was related to tumour blood flow distribution and blood flow response to ATll using an autoradiographic approach. ATll (0.2 pg kg-I * min-I) increased mean arterial blood pressure of anaesthetized BD9 rats from 92.2 f 1. 4 mmHg to 145.6 f 1.3 mmHg. Despite this increase in perfusion pressure, overall tumour blood flow to viable regions decreased by 2Ooh, indicating significant constriction of tumour blood vessels. Autoradiographic localisation of tumour blood flow showed that the decrease in flow was confined to the turnour periphery, with no change at the tumour centre. This pattern was consistent with 10% more binding sites for ATll at the tumour periphery than at the tumour centre. Maximum number of binding sites (BhU) for the P22 turnour was 0.38 f 0.09 fmolmg-I, which is approximately a factor of 10 lower than published values for various normal tissues. The dissociation constant K,, was I. 16 f 0. I8 nM. These results encourage the development of techniques for analysis of receptor binding characteristics for predicting the response of individual turnours to blood flow manipulation using vasoactive agents.