Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature

Karen S. Mark, Amanda R. Burroughs, Rachel C. Brown, Jason D. Huber, Thomas P Davis

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Ischemic stroke from a reduction in blood flow to the brain microvasculature results in a subsequent decreased delivery of oxygen (i.e., hypoxia) and vital nutrients to endothelial, neuronal, and glial cells. Hypoxia associated with stroke has been shown to increase paracellular permeability of the blood-brain barrier, leading to the release of cellular mediators and brain tissue injury. Whereas reperfusion does not occur in all ischemic strokes, increased permeability has been seen in posthypoxic reoxygenation. Currently, it is unknown whether these deleterious effects result from cellular mechanisms stimulated by decreased oxygen during stroke or posthypoxic reoxygenation stress. This study used primary bovine brain microvessel endothelial cells (BBMECs) to examine the involvement of nitric oxide (NO) as a mediator in hypoxia-induced permeability changes. Hypoxia-induced increased transport of [14C]sucrose across BBMEC monolayers compared with normoxia was attenuated by either posthypoxic reoxygenation or inhibition of NO synthase (NOS). The hypoxia-induced permeability effect was further reduced when NOS inhibition was combined with posthypoxic reoxygenation. Additionally, a significant increase in total NO was seen in BBMECs after hypoxic exposure. This correlation was supported by the increased [14C]sucrose permeability observed when BBMECs were exposed to the NO donor diethylenetriaamine NONOate. Western blot analyses of NOS isoforms showed a significant increase in the inducible isoform after hypoxic exposure with a subsequent reduction in expression on reoxygenation. Results from this study suggest that hypoxia-induced blood-brain barrier breakdown can be diminished by inhibition of NO synthesis, decreased concentration of NO metabolites, and/or reoxygenation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number1 55-1
StatePublished - Jan 2004

Fingerprint

Microvessels
Permeability
Nitric Oxide
Endothelial Cells
Stroke
Nitric Oxide Synthase
Brain
Blood-Brain Barrier
Sucrose
Protein Isoforms
Oxygen
Nitric Oxide Donors
Neuroglia
Brain Injuries
Reperfusion
Hypoxia
Western Blotting
Food

Keywords

  • Blood-brain barrier
  • Endothelial
  • Nitric oxide synthase
  • Reoxygenation

ASJC Scopus subject areas

  • Physiology

Cite this

Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature. / Mark, Karen S.; Burroughs, Amanda R.; Brown, Rachel C.; Huber, Jason D.; Davis, Thomas P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 1 55-1, 01.2004.

Research output: Contribution to journalArticle

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