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 t he effect of glutamate on permeability and reactivity of the cerebral microcirculation. The second goal of this study was to determine a pos sible role for nitric oxide in the effects of glutamate on the cerebra l microcirculation. Methods We examined the pial microcirculation in r ats with intravital microscopy. Permeability of the blood-brain barrie r was quantified by the clearance of fluorescent-labeled dextran (mole cular weight, 10 000 D; FITC-dextran-10K) before and during applicatio n of glutamate (0.1 and 1.0 mmol/L). In addition, we examined the perm eability of the blood-brain barrier during application of a nitric oxi de donor, S-nitroso-acetyl-penicillamine (SNAP; 10 mu mol/L). Diameter of pial arterioles was measured before and during application of glut amate or SNAP. To determine a potential role for nitric oxide in gluta mate-induced effects on the cerebral microcirculation, we examined the effects of N-G-monomethyl-L-argininc (10 mu mol/L). Results in contro l rats, clearance from pial vessels was minimal, arterioles remained c onstant during the experimental period. Topical application of glutama te (0.1 and 1.0 mmol/L) and SNAP (10 mu mol/L) produced an increase in clearance of FITC-dextran-10K and in diameter of pial arterioles. In addition, N-G-monomethyl-L-argininc (10 mu mol) attenuated glutamate-i nduced increases in permeability of the blued-brain barrier and glutam ate-induced dilatation of cerebral arterioles. Conclusions The finding s of the present study suggest that glutamate, a major neurotransmitte r in the brain, increases permeability of the blood-brain barrier to l ow-molecular-weight molecules and dilates cerebral arterioles via a ni tric oxide-dependent mechanism.