Renal D-amino acid oxidase mediates chiral inversion of NG-nitro-D-arginine

N-G-nitro-D-arginine (D-NNA), i.v. injected into rats, produced a pressor response, and was presumed to act via chiral inversion into N-G-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. We examined the possible role of renal D-amino acid oxidase (DAAO) in the chiral inversion of D-NNA to L-NNA. In pentobarbital-anesthetized rats, L-NNA was detected via capillary electrochromatography in the blood immediately after i.v. injection of D-NNA. The time course of appearance of L-NNA paralleled the increase in blood pressure elicited by D-NNA. Unilateral renal ligation partially, and bilateral ligation completely, blocked the pressor response as well as the conversion of D-NNA to L-NNA. Furthermore, injection into conscious rats of sodium benzoate, a selective DAAO inhibitor, completely blocked the pressor response to naive D-NNA, but not pressor response to D-NNA preincubated with homogenates of the kidney. Homogenates of the kidneys, liver (lesser degree), and brain (much lesser degree) converted D-NNA to L-NNA, and the chiral inversion was blocked by the addition of benzoate. Moreover, D-NNA chiral inversion correlates with the activity of DAAO. Our results reveal a novel pathway of chiral inversion of D-amino acids where the renal DAAO plays an essential role that accounts for the biological activity of D-NNA.