Characterization of cell selectivity of two 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. NG-Cyclopropyl-L-arginine selectively inhibited Ca2+/calmodulin-dependent NO synthesis, with an IC50 of 0.55 microM in brain versus 184 and 258 microM in macrophages and vascular smooth muscle cells, respectively. In contrast, NG-amino-L-homoarginine blocked NO production by all of the cell types examined, with IC50 values ranging from 6.6 to 26 microM. Both inhibitors were active in an in vivo model of endotoxic shock.
Lambert
L E
LE
Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
French
J F
JF
Whitten
J P
JP
Baron
B M
BM
McDonald
I A
IA
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D006709:Homoarginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology
C073754:omega-N-cyclopropylarginine; C076723:omega-N-aminohomoarginine; D006709:Homoarginine; D009569:Nitric Oxide; D001120:Arginine