Premium
A comparative study of tumour‐blood‐flow modification in two rat‐tumour systems using endothelin‐1 and angiotensin II: Influence of tumour size on angiotensin‐II response
Author(s) -
Bell Katrina M.,
Prise Vivien E.,
Shaffi Katija M.,
Chaplin David J.,
Tozer Gillian M.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960904)67:5<730::aid-ijc23>3.0.co;2-7
Subject(s) - fibrosarcoma , blood flow , angiotensin ii , endocrinology , endothelin receptor , blood vessel , vascular resistance , medicine , receptor , renin–angiotensin system , endothelin 1 , kidney , biology , angiotensin converting enzyme , blood pressure , pathology , chemistry
Tumour‐blood‐flow modification following i.v. administration of angiotensin II (AT II, 0.19 nmol kg − min −1 ) or endothelin‐1 (ET‐1, 1 nmol kg −1 ) was compared in the P22‐carcinosarcoma‐bearing BD9 rat and the HSN‐fibrosarcoma‐bearing CBH/CBi rat using the tissue uptake of radiolabelled iodoantipyrine. Results were compared with a range of normal tissues. HSN tumour blood flow was unmodified by either peptide, whereas 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, skeletal 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 arterial blood pressure ÷ tissue blood flow) in all normal tissues and both tumours, thus demonstrating the existence of vascular receptors for these 2 vasomodifiers, and the capacity of the vessels to respond 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) was unmodified by AT II. Vascular resistance was equally increased in both 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. However, the existence of tumour vascular endothelin receptors suggests that the advent of less toxic and more controllable receptor ligands may make endothelin receptors of value in the modification of tumor blood flow. © 1996 Wiley‐Liss, Inc.