The in vivo unidirectional conversion of nitro-D-arginine to nitro-L-arginine

We recently reported that nitric oxide synthase in the brain can be inhibited not only by nitro-L-arginine (L-NA) but also by its D-enantiomer nitro-D-arginine (D-NA). In the present study, we found that D-NA, when tested in vitro, was 400 times less potent than L-NA. However, when D-NA was injected in vivo, its L-enantiomer, L-NA, was found to rapidly appear in plasma samples (approximately 1 min), rose to a maximum concentration at 30 min (approximately 40% conversion), and remained at this plateau for about 5 h. This was consistent with the changes in blood pressure. There was no conversion of L- to D-NA. The results suggested that D-NA has very weak biological actions by itself, but when administered in vivo, D-NA can be converted to L-NA.