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Nitric oxide-induced perturbations in a cell culture model of the blood-brain barrier

✍ Scribed by R.D. Hurst; I.B. Fritz

Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
649 KB
Volume
167
Category
Article
ISSN
0021-9541

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✦ Synopsis

The actions of an intracellular nitric oxide generator compound on the properties of a co-culture model of the blood-brain barrier are described. Addition of the iron-sulphur cluster nitrosyl Roussin's black salt (RBS, heptanitrosyl-tri-p3-thioxo- tetraferrate (1-1) resulted in a rapid and dose-dependent (50-250 pM) decline in the electrical resistance displayed by co-cultures of vascular endothelial cells and C6 glioma cells. The breach in barrier integrity elicited by RBS (250 pM) could be prevented by either haemoglobin (100 pM), methylene blue (200 pM), or by photon-induced inactivation of RBS. In contrast, the nitric oxide synthase inhibitor nitro-L-arginine methyl ester (250 pM) caused no inhibition in the decline in resistance of RBS-exposed cultures. Addition of 8-bromo-guanosine-cycl ic monophosphate (500 FM) did not mimic the actions of RBS. Exposure to intense light of co-cultures manifesting a high transcellular electrical resistance resulted in a reduction in tissue resistance which could be prevented by the presence of haemoglobin (100 pM). We conclude that nitric oxide liberated from RBS results in a reversible diminution in the integrity of the endothelial cell barrier in the co-culture system, and we suggest that light-sensitive endogenous nitric oxide generator compounds may be present in intact cells. Possible roles of nitric oxide in blood-brain-barrier function are considered.

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