Interactions between L-arginine and L-glutamine change endothelial NO production: An effect independent of NO synthase substrate availability

Jean François Arnal, Thomas Münzel, Richard C. Venema, Natalie L. James, Chang Li Bai, William E. Mitch, David G. Harrison

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2565-2572
Number of pages8
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 1995
Externally publishedYes


  • arginine
  • endothelial cell
  • glutamine
  • nitric oxide synthase

ASJC Scopus subject areas

  • General Medicine


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