Reduced Capacity of Tumour Blood Vessels to Produce Endothelium-derived Relaxing Factor: Significance for Blood Flow Modification

Overview

Journal Br J Cancer

Specialty Oncology

Date 1996 Dec 1

PMID 8980396

Citations 6

Authors

G M Tozer

V E Prise

K M Bell

M F Dennis

M R Stratford

D J Chaplin

Affiliations

Soon will be listed here.

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.

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References

Maragos C, Wang J, Hrabie J, Oppenheim J, Keefer L . Nitric oxide/nucleophile complexes inhibit the in vitro proliferation of A375 melanoma cells via nitric oxide release. Cancer Res. 1993; 53(3):564-8. View

Wood P, Stratford I, Adams G, Szabo C, Thiemermann C, Vane J . Modification of energy metabolism and radiation response of a murine tumour by changes in nitric oxide availability. Biochem Biophys Res Commun. 1993; 192(2):505-10. DOI: 10.1006/bbrc.1993.1444. View

Sagar S, KLASSEN G, Barclay K, Aldrich J . Tumour blood flow: measurement and manipulation for therapeutic gain. Cancer Treat Rev. 1993; 19(4):299-349. DOI: 10.1016/0305-7372(93)90009-g. View

Thomsen L, Lawton F, Knowles R, Beesley J, Moncada S . Nitric oxide synthase activity in human gynecological cancer. Cancer Res. 1994; 54(5):1352-4. View

Buttery L, Springall D, Andrade S, Hart I, Piper P, Polak J . Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. J Pathol. 1993; 171(4):311-9. DOI: 10.1002/path.1711710412. View

Kennovin G, Flitney F, Hirst D . "Upstream" modification of vasoconstrictor responses in rat epigastric artery supplying an implanted tumour. Adv Exp Med Biol. 1994; 345:411-6. DOI: 10.1007/978-1-4615-2468-7_54. View

Chhatwal V, Ngoi S, Chan S, Chia Y, Moochhala S . Aberrant expression of nitric oxide synthase in human polyps, neoplastic colonic mucosa and surrounding peritumoral normal mucosa. Carcinogenesis. 1994; 15(10):2081-5. DOI: 10.1093/carcin/15.10.2081. View

Tozer G, Shaffi K, Prise V, Cunningham V . Characterisation of tumour blood flow using a 'tissue-isolated' preparation. Br J Cancer. 1994; 70(6):1040-6. PMC: 2033701. DOI: 10.1038/bjc.1994.445. View

Wood P, SANSOM J, Butler S, Stratford I, Cole S, Szabo C . Induction of hypoxia in experimental murine tumors by the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Cancer Res. 1994; 54(24):6458-63. View

10.

Zygmunt P, Hogestatt E, Grundemar L . Light-dependent effects of zinc protoporphyrin IX on endothelium-dependent relaxation resistant to N omega-nitro-L-arginine. Acta Physiol Scand. 1994; 152(2):137-43. DOI: 10.1111/j.1748-1716.1994.tb09793.x. View

11.

Cobbs C, Brenman J, Aldape K, Bredt D, Israel M . Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res. 1995; 55(4):727-30. View

12.

Poston L, Taylor P . Glaxo/MRS Young Investigator Prize. Endothelium-mediated vascular function in insulin-dependent diabetes mellitus. Clin Sci (Lond). 1995; 88(3):245-55. DOI: 10.1042/cs0880245. View

13.

FURCHGOTT R, Zawadzki J . The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288(5789):373-6. DOI: 10.1038/288373a0. View

14.

Denekamp J, Hobson B . Endothelial-cell proliferation in experimental tumours. Br J Cancer. 1982; 46(5):711-20. PMC: 2011157. DOI: 10.1038/bjc.1982.263. View

15.

Chaplin D, Acker B . The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069: evidence for therapeutic gain. Int J Radiat Oncol Biol Phys. 1987; 13(4):579-85. DOI: 10.1016/0360-3016(87)90075-7. View

16.

Chaplin D . Hydralazine-induced tumor hypoxia: a potential target for cancer chemotherapy. J Natl Cancer Inst. 1989; 81(8):618-22. DOI: 10.1093/jnci/81.8.618. View

17.

Dvorak H, Nagy J, Dvorak A . Structure of solid tumors and their vasculature: implications for therapy with monoclonal antibodies. Cancer Cells. 1991; 3(3):77-85. View

18.

PETERSON H . Modification of tumour blood flow--a review. Int J Radiat Biol. 1991; 60(1-2):201-10. DOI: 10.1080/09553009114551851. View

19.

Bates J, Baker M, Guerra Jr R, Harrison D . Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required. Biochem Pharmacol. 1991; 42 Suppl:S157-65. DOI: 10.1016/0006-2952(91)90406-u. View

20.

Horsman M, Christensen K, Overgaard J . Relationship between the hydralazine-induced changes in murine tumor blood supply and mouse blood pressure. Int J Radiat Oncol Biol Phys. 1992; 22(3):455-8. DOI: 10.1016/0360-3016(92)90852-9. View