N omega-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation.
Endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells was assayed by examining changes in cyclic GMP levels of rat lung fibroblasts. N omega-nitro-L-arginine and NG-monomethyl-L-arginine inhibited basal and A23187-, ATP- and melittin-induced EDRF release, and the inhibition was prevented with L-arginine. The IC50 values of N omega-nitro-L-arginine and NG-monomethyl-L-arginine for EDRF release evoked with 1 microM A23187 were 230 nM and 16 microM, respectively. N omega-nitro-L-arginine and NG-monomethyl-L-arginine did not affect cyclic GMP accumulation in the fibroblasts with atrial natriuretic factor or sodium nitroprusside. Thus, N omega-nitro-L-arginine is 70 times more potent than NG-monomethyl-L-arginine as a specific inhibitor of EDRF formation/release.
Ishii
K
K
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Chang
B
B
Kerwin
J F
JF
Huang
Z J
ZJ
Murad
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D003864:Depression, Chemical; D005347:Fibroblasts / Q000378:metabolism; D066298:In Vitro Techniques; D008555:Melitten / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine
D008555:Melitten; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D000255:Adenosine Triphosphate; D001120:Arginine; D013482:Superoxide Dismutase; D006152:Cyclic GMP