title: Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier.
abstract: The goal of the present study was to determine the role of basal synthesis/release of nitric oxide on the basal permeability characteristics of the blood-brain barrier to various sized molecules in vivo. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier was quantitated by calculating the clearance of fluorescent-labeled albumin (mol.wt.=69,000 Da; FITC-albumin), fluorescent-labeled dextran (mol.wt.=10,000 Da; FITC-dextran-10K) or sodium fluorescein (mol.wt.=376; NaFl) in the absence and presence of an inhibitor of nitric oxide synthase (N(G)-monomethyl-L-arginine; L-NMMA; 10 and 100 microM). During superfusion with vehicle, clearance of FITC-albumin, FITC-dextran-10K and NaFl from pial vessels and diameter of pial arterioles remained constant. To determine whether basal synthesis/release of nitric oxide affected basal permeability of the blood-brain barrier, we examined the effects of L-NMMA (10 and 100 microM). In addition, we examined the adherence of leukocytes to cerebral venular endothelium using rhodamine 6G. Although topical application of L-NMMA produced constriction of pial arterioles, L-NMMA did not alter the permeability characteristics of the blood-brain barrier to FITC-albumin, FITC-dextran-10K or NaFl. Further, the adherence of leukocytes to the endothelium appeared to be similar while suffusing with vehicle and L-NMMA (100 microM). Thus, the findings of the present study suggest that while basal synthesis/release of nitric oxide may play an important role in regulation of basal tone of cerebral blood vessels, it does not appear that basal synthesis/release of nitric oxide plays an important role in maintaining the integrity of the blood-brain barrier to large or small molecules.
authors.affiliation: Department of Physiology and Biophysics, 984575 Nebraska Medical Center, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-4575, USA. wgmayhan@unmc.edu
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003911:Dextrans / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010841:Pia Mater / Q000098:blood supply; D051381:Rats; D011920:Rats, Inbred WF; D012235:Rhodamines / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D003911:Dextrans; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D012235:Rhodamines; C039217:fluorescein isothiocyanate bovine serum albumin; C015219:fluorescein isothiocyanate dextran; C026188:rhodamine 6G; D012710:Serum Albumin, Bovine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D016650:Fluorescein-5-isothiocyanate