ROLE OF NITRIC-OXIDE IN HISTAMINE-INDUCED INCREASES IN PERMEABILITY OF THE BLOOD-BRAIN-BARRIER

While previous studies have examined the effects of histamine on the p ermeability of the blood-brain barrier and reactivity of cerebral bloo d vessels, cellular mechanisms which account for histamine-induced aff ects on the cerebral microcirculation are not clear. The goals of this study were to determine the role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier and dilatation o f pial arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain b arrier (clearance of fluorescent-labeled dextran; molecular weight 10, 000 daltons; FITC-dextran-10K) and diameter of pial arterioles were me asured in the absence and presence of histamine (10 and 100 mu M). Dur ing superfusion with vehicle (saline), clearance of FITC-dextran-10K f rom pial vessels was minimal and diameter of pial arterioles remained constant. Topical application of histamine (10 and 100 mu M) produced an increase in clearance of FITC-dextran-10K and diameter of pial arte rioles. To determine a potential role for nitric oxide in histamine-in duced increases in permeability of the blood-brain barrier and dilatat ion of pial arterioles, we examined the effects of N-G-monomethyl-L-ar ginine (L-NMMA; 10 mu M). L-NMMA inhibited histamine-induced increases in permeability of the blood-brain barrier and attenuated histamine-i nduced dilatation of cerebral arterioles. The findings of the present study suggest that histamine increases permeability of the blood-brain barrier and diameter of pial arterioles via the synthesis/release of nitric oxide or a nitric oxide containing compound.