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 language | English (US) |
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Pages (from-to) | A486 |
Journal | FASEB Journal |
Volume | 11 |
Issue number | 3 |
State | Published - Dec 1 1997 |
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics