Glutamate-induced disruption of the blood-brain barrier in rats. Role of nitric oxide.

BACKGROUND AND
PURPOSE: The first goal of this study was to determine the effect of glutamate on permeability and reactivity of the cerebral microcirculation. The second goal of this study was to determine a possible role for nitric oxide in the effects of glutamate on the cerebral microcirculation.
METHODS: We examined the pial microcirculation in rats with intravital microscopy. Permeability of the blood-brain barrier was quantified by the clearance of fluorescent-labeled dextran (molecular weight, 10 000 D; FITC-dextran-10K) before and during application of glutamate (0.1 and 1.0 mmol/L). In addition, we examined the permeability of the blood-brain barrier during application of a nitric oxide donor, S-nitroso-acetyl-penicillamine (SNAP; 10 mumol/L). Diameter of pial arterioles was measured before and during application of glutamate or SNAP. To determine a potential role for nitric oxide in glutamate-induced effects on the cerebral microcirculation, we examined the effects of NG-monomethyl-L-arginine (10 mumol/L).
RESULTS: In control rats, clearance of FITC-dextran-10K from pial vessels was minimal, and the diameter of pial arterioles remained constant during the experimental period. Topical application of glutamate (0.1 and 1.0 mmol/L) and SNAP (10 mumol/L) produced an increase in clearance of FITC-dextran-10K and in diameter of pial arterioles. In addition, NG-monomethyl-L-arginine (10 mumol) attenuated glutamate-induced increases in permeability of the blood brain barrier and glutamate-induced dilatation of cerebral arterioles.
CONCLUSIONS: The findings of the present study suggest that glutamate, a major neurotransmitter in the brain, increases permeability of the blood-brain barrier to low-molecular-weight molecules and dilates cerebral arterioles via a nitric oxide-dependent mechanism.