NG-amino-L-arginine: a new potent antagonist of L-arginine-mediated endothelium-dependent relaxation.
This study examined the influence of NG-amino-L-arginine, a novel structural analog of L-arginine, on endothelium-dependent relaxation, contraction, and cyclic GMP accumulation in isolated rings of bovine pulmonary artery. NG-Amino-L-arginine caused potent and stereoselective endothelium-dependent contraction that was associated with a marked and endothelium-dependent decline in basal levels of cyclic GMP in smooth muscle. NG-Amino-L-arginine caused concentration-dependent, competitive, and stereoselective antagonism of acetylcholine-elicited relaxation and cyclic GMP accumulation. NG-Amino-L-arginine was 100- to 300- fold more potent than NG-methyl-L-arginine and did not inhibit endothelium-independent relaxation elicited by nitroglycerin. This potent inhibitory analog of L-arginine should be a useful chemical probe for studying the biosynthesis and biological role of L-arginine-derived nitric oxide both in vitro and in vivo.
Fukuto
J M
JM
Department of Pharmacology, UCLA School of Medicine.
Wood
K S
KS
Byrns
R E
RE
Ignarro
L J
LJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D004727:Endothelium / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology
C063904:N(G)-aminoarginine; D001120:Arginine; D006152:Cyclic GMP