Pial arteriolar dilation to acetylcholine is inhibited by ammonia-induced increases in glutamine

T. Kawaguchi, R. C. Koehler, S. W. Brusilow, R. J. Traystman

Research output: Contribution to journalArticlepeer-review


Glutamine can inhibit acetylcholine (Ach) induced NO synthesis in aortic endothelial cells. We tested whether increases in brain glutamine induced by hyperammonemia inhibits Ach vasodilation. In five groups (n=8) of pentobarbital-anesthetized rats, pial arteriolar diameter response to 3 × 10-5 M Ach was measured through a cranial window before and at 6h iv infusion of either sodium acetate (NaAc; plasma ammonia = 45 ± 10 μM; ± SE) or ammonium acetate (NH4Ac; plasma ammonia = 642 ± 84 μM). Dilation to Ach was unchanged by NaAc infusion (13±1% pre-infusion to 16±1% post-infusion). NH4Ac infusion increased cortical glutamine concentration threefold (7.5±0.7 vs 27±2 μmol/g) and inhibited Ach vasodilation (16±2 to 0±2%). To dissociate the effects of glutamine from NH4+ ions, the glutamine synthetase inhibitor methionine sulfoximine (MSO; 150 mg/kg, iv) was infused 3h before NaAc or NH4Ac infusion. MSO prevented the increase in tissue glutamine and the loss of Ach vasodilation (10±1 to 11±2%) during NH4Ac infusion. With MSO pretreatment before NaAc infusion, the Ach response was also unchanged (12±1 to 9±2%). Infusion of L-arginine (2 mmol/kg/h) during the last 2h of the 6h NH4Ac infusion partially attenuated the decrease in the Ach response (16±2 to 7±1%). We conclude that ammonia-induced increases in glutamine are capable of inhibiting Ach evoked vasodilation in pial arterioles and that L-arginine can partially reverse the inhibitory effect of glutamine.

Original languageEnglish (US)
Pages (from-to)A486
JournalFASEB Journal
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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