Brain nitric oxide inactivation is governed by the vasculature

Ricardo M. Santos, Cátia F. Lourenço, François Pomerleau, Peter Huettl, Greg A. Gerhardt, João Laranjinha, Rui M. Barbosa

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The mechanisms underlying nitric oxide (NO) synthesis and inactivation in the brain are essential determinants of NO neuroactivity. Although NO production is well characterized, the pathways of inactivation in vivo remain largely unknown. Here, we characterize the kinetics and the major mechanism of NO inactivation in the rat brain cortex and hippocampus in vivo by measuring locally applied NO with carbon-fiber microelectrodes (CFMs) and ceramic-based microelectrode arrays (MEAs). An apparent first-order clearance was observed in both brain regions, with decay rate constants (k) of NO signals of 0.67 to 0.84 per second, significantly higher than the k obtained in agarose gel (0.099 per second), used as a NO diffusion-control medium. NO half-life in vivo, estimated by mathematical modeling, was 0.42 to 0.75 s. Experiments using MEAs support that the NO diffusion radius is heterogeneous and related to local metabolic activity and vascular density. After global ischemia, k decreased to control values of diffusion in gel, but during anoxia, k decreased only 21%. Additionally, k in brain slices was threefold to fivefold lower than that in vivo, and hemorrhagic shock induced a 53% decrease in k. Overall, the results support that NO scavenging by circulating erythrocytes constitutes the major NO-inactivation pathway in the brain.

Original languageEnglish
Pages (from-to)1011-1021
Number of pages11
JournalAntioxidants and Redox Signaling
Issue number6
StatePublished - Mar 15 2011

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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