Fluctuations in Tumor Blood Flow under Normotension and the Effect of Angiotensin II‐induced Hypertension

Abstract

To elucidate the significance of angiotensin II (AID‐induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly‐developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All‐induced hypertension seemed to be greater than that under normotension, because the All‐increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no‐flow or low‐flow areas, resistant to delivery of anti‐cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All‐induced hypertension.

A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs

“…were given at 90-min intervals to maintain immobilization during the experiment. Enflurane concentration was maintained at 1% in the inhaled carrier gas at 1 l min 71 by means of an anaesthetic apparatus for small laboratory animals (Hori et al, 1991).…”

“…TBF was measured with the hydrogen clearance method (Hori et al, 1991(Hori et al, , 1996 whose principle was described in detail by Aukland et al (1964). In brief, after saturation of the tissue with hydrogen following inhalation of 9% hydrogen gas in air (at 1 l min 71 ), the blood flow value (in ml min 71 100 g 71 tissue) was calculated from the half-life of the clearance curve obtained.…”

The response of tumour vasculature to angiotensin II revealed by its systemic and local administration to 'tissue-isolated' tumours

“…However, in absolute terms, ATII has been found to increase blood flow in some tumours (Tokuda et al. 1990; Honr et al, 1991;Tanda et al, 1991) while decreasing it in others (Jirtle et al, 1978;Tozer and Shaffi, 1993). A decrease in absolute tumour blood flow could compromise delivery of drug to tumour microregions.…”

Modification of tumour blood flow using the hypertensive agent, angiotensin II

“…Later, Jirtle et al (1978) found that constant intravenous infusion of high dose angiotensin 11 (1.4 Ag min ') into tumour-bearing rats caused a 4-fold increase in blood flow to the tumour growing in the mammary gland relative to that in the normal mammary gland and skin although the absolute blood flow to the tumour was decreased from 1.3 ml g -min ' to 0.8 ml g' min-'. Subsequent studies have shown that angiotensin IIinfusion can increase absolute, as well as relative, blood flow in some tumour systems (Tokuda et al, 1990;Hori et al, 1991;Tanda et al, 1991;Trotter et al, 1991).…”