Nitric oxide synthesis in the CNS endothelium and macrophages differs in its sensitivity to inhibition by arginine analogues.
Inhibition of nitric oxide production by arginine analogues was examined in three cell systems; macrophages, CNS tissue and endothelial cells. Nitric oxide production was assessed indirectly using in vitro assays measuring nitrite production (macrophages), cGMP elevation (CNS) and acetylcholine-induced relaxation of aortic ring segments (endothelium). NG-monomethyl-L-arginine and NG-amino-L-arginine possessed similar inhibitory activity in all three assays, while NG-nitro-L-arginine displayed a striking selectivity for inhibition of brain and endothelial cell nitric oxide synthesis, with IC50 values of 0.05 microM in the CNS versus 200 microM in macrophages. These results suggest that distinct enzymes are responsible for nitric oxide synthesis in different cell types, and indicate that it may be possible to selectively modulate nitric oxide production in vivo.
Lambert
L E
LE
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Whitten
J P
JP
Baron
B M
BM
Cheng
H C
HC
Doherty
N S
NS
McDonald
I A
IA
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C063904:N(G)-aminoarginine; D016202:N-Methylaspartate; D001120:Arginine; D006152:Cyclic GMP