REDUCED CAPACITY OF TUMOR BLOOD-VESSELS TO PRODUCE ENDOTHELIUM-DERIVED RELAXING FACTOR - SIGNIFICANCE FOR BLOOD-FLOW MODIFICATION

The effect of nitric oxide-dependent vasodilators on vascular resistan ce of tumours and normal tissue was determined with the aim of modifyi ng tumour blood flow for therapeutic benefit. isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused es vivo. The effects on tissue vascular resistance of administration of sodium nit roprusside (SNP) and the diazeniumdiolate (or NONO-ate) NOC-7, vasodil ators which act via direct release of nitric oxide (NO), were compared with the effects of acetylcholine (ACh), a vasodilator which acts pri marily 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 ph enylephrine (PE) or potassium chloride (KCI) as indicated by a decreas e in vascular resistance. SNP also effectively dilated normal rat hind limb vessels after PE/KCl constriction. Vasodilatation in the tumour p reparations was accompanied by a significant rise in nitrite levels me asured 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 incapab le of releasing NO (EDRF) in response to ACh. Capacity for EDRF produc tion may represent a difference between tumour and normal tissue blood vessels, which could be exploited for selective pharmacological manip ulation of tumour blood flow.