EFFECT OF LIPOPOLYSACCHARIDE ON THE PERMEABILITY AND REACTIVITY OF THE CEREBRAL MICROCIRCULATION - ROLE OF INDUCIBLE NITRIC-OXIDE SYNTHASE

The goal of this study was to examine the effect of lipopoly saccharid e on the permeability of the blood-brain barrier and reactivity of cer ebral arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain ba rrier (clearance of fluorescent-labeled dextran; molecular weight 10,0 00 Da; FITC-dextran-10K) and diameter of pial arterioles were measured in the absence and presence of topical application of vehicle (saline ) or lipopolysaccharide (200 ng/ml). During superfusion with vehicle, clearance of FITC-dextran-10K from pial vessels was minimal, and diame ter of pial arterioles remained constant. Topical application of Lipop olysaccharide (200 ng/ml) produced an increase in clearance of FITC-de xtran-10K and dilated pial arterioles. To determine whether lipopolysa ccharide-induced changes in permeability of the blood-brain barrier an d dilatation of cerebral arterioles was related to the synthesis/relea se of inducible nitric oxide, we examined the effects of aminoguanidin e (0.5 mM). Aminoguanidine inhibited lipopolysaccharide-induced increa ses in permeability of the blood-brain barrier and dilatation of cereb ral arterioles. The findings of the present study suggest that lipopol ysaccharide increases permeability of the blood-brain barrier and diam eter of pial arterioles via the activation of inducible nitric oxide s ynthase. (C) 1998 Elsevier Science B.V.