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.
Wang
Q
Q
Department of Anesthesiology, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
Cwik
M
M
Wright
C J
CJ
Cunningham
F
F
Pelligrino
D A
DA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase