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

Abstract

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
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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