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 saccharide 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.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA. wgmayhan@mail.unmc.edu
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D001424:Bacterial Infections / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003911:Dextrans / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D010841:Pia Mater / Q000098:blood supply / Q000201:enzymology; D051381:Rats; D011920:Rats, Inbred WF; D014699:Venules / Q000187:drug effects / Q000201:enzymology
D003911:Dextrans; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; C015219:fluorescein isothiocyanate dextran; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D016650:Fluorescein-5-isothiocyanate; C004479:pimagedine