Interactions between L-arginine and L-glutamine change endothelial NO production. An effect independent of NO synthase substrate availability.
The effect of extracellular L-arginine and L-glutamine on nitric oxide (NO) release was studied in cultured bovine aortic endothelial cells and in rabbit aortic rings. Increasing L-arginine (0.01 to 10 mM) did not alter NO release from cultured endothelial cells or modify endothelium-dependent relaxation to acetylcholine in isolated vessels. L-Glutamine (0.6 and 2 mM) inhibited NO release from cultured cells (in response to bradykinin) and from aortic rings (in response to acetylcholine or ADP). L-Arginine (0.1-10 mM) dose-dependently reversed the L-glutamine inhibition of receptor-stimulated NO release in both models. In contrast to its inhibitory response to receptor-mediated stimuli, glutamine alone slightly potentiated NO release in both models when the calcium ionophore, A23187, was added. Furthermore, cultured cells incubated with L-arginine (0.01-10 mM), in the presence or absence of glutamine, released similar amounts of NO in response to A23187. L-Glutamine did not affect intracellular L-arginine levels. Neither D-glutamine nor D-arginine affected NO release or endothelium-dependent vascular relaxation. L-Glutamine had no effect on the activity of endothelial NOS assessed by L-arginine to L-citrulline conversion. These findings show that in the absence of L-glutamine, manipulating intracellular L-arginine levels over a wide range does not affect NO release. L-Glutamine in concentrations circulating in vivo may tonically inhibit receptor-mediated NO release by interfering with signal transduction. One mechanism by which L-arginine may enhance NO release is via reversal of the inhibitory effect of L-glutamine, but apparently independently of enhancing NO synthase substrate.
Arnal
J F
JF
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Münzel
T
T
Venema
R C
RC
James
N L
NL
Bai
C L
CL
Mitch
W E
WE
Harrison
D G
DG
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects
D012333:RNA, Messenger; D005973:Glutamine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine