Nitric oxide donor-induced increase in permeability of the blood-brain barrier

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Abstract

The goal of the present study was to determine the effect of nitric oxide (NO) donors on the permeability of the blood-brain barrier 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 dextran (M(w)=10 000 Da; FITC-dextran-10K) during suffusion with vehicle, S-nitroso-N-acetylpenicillamine (SNAP; 100 μM) and 3-morpholinosydnonimin (SIN-1; 100 μM). In addition, we examined changes in arteriolar diameter during suffusion with vehicle, SNAP and SIN-1. During suffusion with vehicle, clearance of FITC-dextran-10K from pial vessels and diameter of pial arterioles remained relatively constant during the experimental period. In contrast, suffusion with SNAP or SIN-1 markedly increased clearance of FITC-dextran-10K from the cerebral microcirculation and produced a rapid, sustained dilatation of pial arterioles. Thus, NO donors increase the permeability of the blood-brain barrier and produce pronounced dilatation of cerebral arterioles. In light of evidence suggesting that NO donors may produce their effect by the simultaneous release of NO and superoxide anion to form peroxynitrite, we elected to examine the role of superoxide anion in increases in permeability of the blood-brain barrier in response to SNAP and SIN-1. We found that suffusion with tiron (1 mM) did not alter basal permeability of the blood-brain barrier, but significantly inhibited increases in permeability of the blood-brain barrier in response to SNAP and SIN-1. In addition, tiron did not alter baseline diameter of cerebral arterioles, or SNAP- and SIN-1-induced cerebrovasodilatation. The findings of the present study suggest that NO donors produce an increase in permeability of the blood-brain barrier which appears to be related to the presence of NO and superoxide anion, to presumably form peroxynitrite. We suggest that increases in NO formation observed during brain trauma may contribute to disruption of the blood-brain barrier. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalBrain Research
Volume866
Issue number1-2
DOIs
StatePublished - Jun 2 2000

Fingerprint

Nitric Oxide Donors
Blood-Brain Barrier
Permeability
Arterioles
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Superoxides
Nitric Oxide
Peroxynitrous Acid
Microcirculation
Dilatation
S-Nitroso-N-Acetylpenicillamine
Dextrans
Fluorescence Microscopy

Keywords

  • Cerebral venules
  • FITC-dextran
  • Nitric oxide
  • Peroxynitrite
  • Pial arterioles
  • SIN-1
  • SNAP
  • Superoxide anion
  • Tiron

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Nitric oxide donor-induced increase in permeability of the blood-brain barrier. / Mayhan, William G.

In: Brain Research, Vol. 866, No. 1-2, 02.06.2000, p. 101-108.

Research output: Contribution to journalArticle

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