EFFECTS OF NITRIC-OXIDE MODULATION ON TUMOR BLOOD-FLOW AND MICROVASCULAR PERMEABILITY IN C6 GLIOMA

C6 glioma strongly express nitric oxide synthase. Rats bearing C6 tumo urs were pre-treated with i.v. N-g-nitro-L-arginine methyl ester (L-NA ME), 3-morpholinosydnonimine (SIN-1) or saline before local cerebral b lood flow (LCBF) or tumour capillary permeability (TCP) was measured b y the [C-14]iodoantipyrine autoradiographic or [C-14]alpha-amino-isobu tyric acid techniques. L-NAME and SIN-1 caused significant TBF alterat ions (-44% and +136%, respectively) with less marked (-15% and +33%) a lterations in normal brain. Calculated cerebrovascular resistance chan ges within tumour were indeed selective. Baseline TCP was increased co mpared with normal brain (20-fold). L-NAME and SIN-1 administration di d not alter TCP. These effects have significant implications for human malignant glioma management. Selective i.v. manipulation of LCBF, wit hout significant changes in TCP, could increase the efficacy of chemot herapy, radiotherapy or provide better peritumoural oedema control. (C ) 1998 Rapid Science Ltd.