7-NITRO INDAZOLE DERIVATIVES ARE POTENT INHIBITORS OF BRAIN, ENDOTHELIUM AND INDUCIBLE ISOFORMS OF NITRIC-OXIDE SYNTHASE

The effect of 7-nitro indazole (7-NI) and a range of substituted indazole derivatives on nitric or;ide synthase (NOS) enzyme activity in homogenates of rat cerebellum, bovine endothelial cells and lung from endotoxin-pretreated rats was investigated. 3-bromo 7-nitro indazole was either equipotent (IC50, 0.86 +/- 0.05 mu M c.f. 0.78 +/- 0.2 mu M, n=6, P>0.05) or approximately 4x (IC50, 0.17 = 0.01 mu M c.f. 0.71 +/- 0.01 mu M, n=6, P<0.05) or 20x(IC50, 0.29 +/- 0.01 mu M c.f. 5.8 +/- 0.4 mu M, n=6, P<0.05) more potent than 7-NI as an inhibitor of bovine endothelial, rat cerebellar and rat lung NOS enzyme activity respectively. 2,7-dinitro indazole also inhibited NOS in all three tissue sources with a potency similar to that of 7-NI. These results suggest that 3-bromo 7-NI and 2,7-dinitro indazole may prove to be useful additional tools with which to examine the biological properties of nitric oxide (NO).