EFFECT OF ANGIOTENSIN-II-INDUCED HYPERTENSION ON TUMOR BLOOD-FLOW ANDINTERSTITIAL FLUID PRESSURE

The effect of angiotensin II-induced hypertension on tumor interstitia l fluid pressure (TIFP) and tumor blood flow (TBF) was investigated to examine blood flow and pressure regulation in solid tumors. TIFP meas urements were made before and after administration of angiotensin II u sing the wick-in-needle method in s.c. tumor implants. Relative TBF wa s continuously monitored by laser doppler velocimetry. The effect or h ost strain on TIFP was evaluated in MCA-IV mammary carcinoma, transpla nted in C3H and SCID mice, and showed no significant difference. The e ffects of tumor types were evaluated by comparing two murine tumors, M CA-IV mammary carcinoma and FSaII fibrosarcoma, and a human tumor xeno graft, LS174T adenocarcinoma, transplanted in SCID mice. Baseline TIFP was elevated in all three tumor lines to significantly different pres sures. AII-induced hypertension (approximately 150 mm Hg) had a variab le but tumor line-specific effect on TIFP and TBF. The increase in TIF P was correlated with the baseline TIFP (r2 = 0.853) (increasing from 6.9 to 8.7 mm Hg, 10.5 to 15.8 mm Hg, and 21.7 to 29.4 mm Hg in FSaII, MCA-IV, and LS174T, respectively). These data suggest that in additio n to blood now redistribution due to the steal phenomenon, arterial co ntrol of TBF and TIFP exists within these solid tumors; however, the e xtent of control is tumor line dependent and less than that in normal tissues. Moreover, parallel increases in TIFP and TBF do not support t he hypothesis that elevated TIFP causes vascular collapse and thus dec reases TBF.