A COMPARATIVE-STUDY OF TUMOR BLOOD-FLOW MODIFICATION IN 2 RAT-TUMOR SYSTEMS USING ENDOTHELIN-1 AND ANGIOTENSIN-II - INFLUENCE OF TUMOR SIZEON ANGIOTENSIN-II RESPONSE

Tumour blood flow modification following i.v. administration of angiot ensin II (AT II, 0.19 nmol kg(-1) min(-1)) or endothelin-I (ET-I, I nm ol kg(-1)) was compared in the P22 carcinosarcoma-bearing BD9 rat and the HSN fibrosarcoma-bearing CBH/CBi rat using the tissue uptake of ra diolabelled iodoantipyrine. Results were compared with a range of norm al tissues. HSN tumour blood flow was unmodified by either peptide, wh ereas P22 tumour blood flow was unmodified by ET-I but was reduced to 80% of the control flow by AT II. Both peptides reduced absolute blood flow in the skin overlying the tumour, in contralateral skin, skeleta l muscle, kidney and small intestine, whereas blood flow to the brain and heart was significantly increased by ET-I and unmodified by AT II. Both peptides significantly increased vascular resistance (mean arter ial blood pressure divided by tissue blood flow) in all normal tissues and both tumours, thus demonstrating the existence of vascular recept ors for these 2 vasomodifiers, and the capacity of the vessels to resp ond to receptor activation. Dependency of response on tumour size was examined in the P22 tumour. In contrast to that in small P22 tumours ( 1.22 +/- 0.06 g), blood flow to large P22 tumours (7.18 +/- 0.25 g) wa s unmodified by AT II. Vascular resistance was equally increased in bo th tumour groups, thus illustrating little difference in the vascular response to AT II in the size range examined. Results show that the 2 rat tumours responded directly to ET-I and AT II, but do not indicate any advantage of ET-I over AT II in tumour blood flow modification. Ho wever, the existence of tumour vascular endothelin receptors suggests that the advent of less toxic and more controllable receptor ligands m ay make endothelin receptors of value in the modification of tumour bl ood flow. (C) 1996 Wiley-Liss, Inc.