Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier

William G. Mayhan

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 μM). 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 μM). 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 μM). 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. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalBrain Research
Volume855
Issue number1
DOIs
StatePublished - Feb 7 2000

Keywords

  • Brain, rat
  • Cerebral venule
  • FITC-albumin
  • FITC-dextran
  • L-NMMA
  • Nitric oxide
  • Pial arteriole
  • Rhodamine 6G
  • Sodium fluorescein

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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