Reversible inactivation of endothelial nitric oxide synthase by NG-nitro-L-arginine.
NG-Methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA) inhibited NO-induced cGMP accumulation in porcine aortic endothelial cells with half-maximally effective concentrations of 15 and 3.4 microM, respectively. The effects of both compounds were reversible, but the L-NNA-induced inhibition was only reversed by wash-out in the presence of 1 mM L-arginine. In short-term incubations (45 s) of membrane fractions, L-NMA and L-NNA exhibited similar potencies to inhibit endothelial NO synthase, but L-NNA was markedly more potent than L-NMA after prolonged incubation periods (> or = 3 min) due to induction of a pronounced, reversible enzyme inactivation.
Mayer
B
B
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Schmid
M
M
Klatt
P
P
Schmidt
K
K
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology*; D007700:Kinetics; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D013552:Swine; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases