Identification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell L-arginine transporter

Abstract

The effects of inhibitors of nitric oxide (NO) synthase and other cationic amino acids on unidirectional L-arginine transport were studied in porcine aortic endothelial cells cultured in microwell plates or perfused in microcarrier columns. L-Homoarginine, L-lysine and L-ornithine inhibited transport of L-arginine. The NO synthase inhibitors NG-monomethyl-L-arginine and NG-iminoethyl-L-ornithine also reduced L-arginine uptake, whereas NG-nitro-L-arginine and its methyl-ester had no inhibitory effect. The ability to modulate selectively endothelial cell L-arginine transport or NO synthase activity will allow further characterization of the arginine transporter and its role in regulating NO biosynthesis.