NW-nitro L-arginine benzyl ester, a potent irreversible inhibitor of endothelium dependent relaxation

In the rat aorta preparation, we have used the nitro-arginine derivative, NW-nitro L-arginine benzyl ester (NABE), as a probe to investigate the relationship between L-arginine and the endothelium derived relaxing factor (EDRF). We find NABE to be a potent endothelium dependent vasoconstrictor and inhibitor of relaxation. The effect of NABE is irreversible and not removed by subsequent washing. The vasoconstrictor effect of NABE differs from other EDRF inhibitors like NG-monomethyl L-arginine (L-NMMA) in that it is not antagonized by pre-treatment with excess L-arginine. In contrast, like other EDRF inhibitors, at high concentration NABE exhibits vasodilation which is antagonized by methylene blue. We suggest that the previous reports on the antagonism between L-arginine and the putative EDRF inhibitors like L-NMMA are due to their structural similarities rather than to externally added L-arginine acting as a substrate for EDRF synthesis.