Tozer, G. M., Prise, V. E., Bell, K. M. et al. (3 more authors) (1996) Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing factor: Significance for blood flow modification. British Journal of Cancer, 74 (12). pp. 1955-1960. ISSN 0007-0920
Abstract
The effect of nitric oxide-dependent vasodilators on vascular resistance of tumours and normal tissue was determined with the aim of modifying tumour blood flow for therapeutic benefit. Isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused ex vivo. The effects on tissue vascular resistance of administration of sodium nitroprusside (SNP) and the diazeniumdiolate (or NONO-ate) NOC-7, vasodilators which act via direct release of nitric oxide (NO), were compared with the effects of acetylcholine (ACh), a vasodilator which acts primarily via receptor stimulation of endothelial cells to release NO in the form of endothelium-derived relaxing factor (EDRF). SNP and NOC-7 effectively dilated tumour blood vessels after preconstriction with phenylephrine (PE) or potassium chloride (KCl) as indicated by a decrease in vascular resistance. SNP also effectively dilated normal rat hindlimb vessels after PE/KCl constriction. Vasodilatation in the tumour preparations was accompanied by a significant rise in nitrite levels measured in the tumour effluent. ACh induced a significant vasodilation in the normal hindlimb but an anomalous vasoconstriction in the tumour. This result suggests that tumours, unlike normal tissues are incapable of releasing NO (EDRF) in response to ACh. Capacity for EDRF production may represent a difference between tumour and normal tissue blood vessels, which could be exploited for selective pharmacological manipulation of tumour blood flow.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1996 Stockton Press. Papers published under this licence are made freely available to all readers under a CC/BY-NC-SA/4.0 licence one year after publication in BJC |
Keywords: | P22 rat carcinosarcoma; tumour vascular resistance; nitric oxide; nitric oxide donors; isolated perfusion; endothelium-derived relaxing factor; NITRIC-OXIDE SYNTHASE; THERAPEUTIC GAIN; MURINE TUMOR; L-ARGININE; HYDRALAZINE; CANCER; PROLIFERATION; VASCULATURE; EXPRESSION; RELAXATION |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Feb 2017 14:44 |
Last Modified: | 16 Feb 2017 14:44 |
Published Version: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20748... |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107969 |