IMPAIRMENT OF OSTEOBLAST GROWTH BY NITRIC-OXIDE SYNTHASE INHIBITORS -AN EFFECT INDEPENDENT OF NITRIC-OXIDE AND ARGININE TRANSPORT INHIBITION

The effect of various inhibitors of nitric oxide synthase (NOS) on thr ee cell lines with osteoblastic phenotype was studied. N-Mono-methyl a rginine (NMMA) inhibited the growth of MG63 and ROS 17/2.8 cells, and N-iminoethyl-ornithine (NIO) inhibited the growth of ROS 17/2.8. Howev er, N-nitro-arginine (NA) and N-nitro-arginine-methyl ester (NAME) had no effect. None of the NOS inhibitors affected MC3T3 growth, in spite of blocking NO synthesis. NMMA and NIO also caused a marked decrease of arginine uptake by the three cell lines studied. These results indi cate that some NOS inhibitors have antiproliferative effects which do not seem to be related to the inhibition of NOS activity or arginine u ptake.