Effect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase

Abstract

The goal of this study was to examine the effect of lipopolysaccharide on the permeability of the blood–brain barrier and reactivity of cerebral arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood–brain barrier (clearance of fluorescent-labeled dextran; molecular weight 10,000 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 diameter of pial arterioles remained constant. Topical application of lipopolysaccharide (200 ng/ml) produced an increase in clearance of FITC-dextran-10K and dilated pial arterioles. To determine whether lipopolysaccharide-induced changes in permeability of the blood–brain barrier and dilatation of cerebral arterioles was related to the synthesis/release of inducible nitric oxide, we examined the effects of aminoguanidine (0.5 mM). Aminoguanidine inhibited lipopolysaccharide-induced increases in permeability of the blood–brain barrier and dilatation of cerebral arterioles. The findings of the present study suggest that lipopolysaccharide increases permeability of the blood–brain barrier and diameter of pial arterioles via the activation of inducible nitric oxide synthase.