CHARACTERIZATION OF CELL SELECTIVITY OF 2 NOVEL INHIBITORS OF NITRIC-OXIDE SYNTHESIS

We have assessed the capacity of two novel inhibitors to block cytokine-induced nitric oxide (NO) synthesis by macrophages and vascular smooth muscle cells, as well as NO production by the constitutive enzyme in central nervous system tissue. N(G)-Cyclopropyl-L-arginine selectively inhibited Ca2+/calmodulin-dependent NO synthesis, with an IC50 of 0.55-mu-M in brain versus 184 and 258-mu-M in macrophages and vascular smooth muscle cells, respectively. In contrast, N(G)-amino-L-homoarginine blocked NO production by all of the cell types examined, with IC50 values ranging from 6.6 to 26-mu-M. Both inhibitors were active in an in vivo model of endotoxic shock.