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 journalArticle

161 Citations (Scopus)

Abstract

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
Volume95
Issue number6
DOIs
StatePublished - Jan 1 1995

Fingerprint

Glutamine
Nitric Oxide Synthase
Arginine
Nitric Oxide
Cultured Cells
Calcimycin
Acetylcholine
Endothelial Cells
Citrulline
Calcium Ionophores
Bradykinin
Vasodilation
Adenosine Diphosphate
Endothelium
Signal Transduction
Rabbits

Keywords

  • arginine
  • endothelial cell
  • glutamine
  • nitric oxide synthase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Interactions between L-arginine and L-glutamine change endothelial NO production : An effect independent of NO synthase substrate availability. / Arnal, Jean François; Münzel, Thomas; Venema, Richard C; James, Natalie L.; Bai, Chang Li; Mitch, William E.; Harrison, David G.

In: Journal of Clinical Investigation, Vol. 95, No. 6, 01.01.1995, p. 2565-2572.

Research output: Contribution to journalArticle

Arnal, Jean François ; Münzel, Thomas ; Venema, Richard C ; James, Natalie L. ; Bai, Chang Li ; Mitch, William E. ; Harrison, David G. / Interactions between L-arginine and L-glutamine change endothelial NO production : An effect independent of NO synthase substrate availability. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 6. pp. 2565-2572.
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abstract = "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.",
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