Neuronal nitric oxide synthase (NOS) regulates leukocyte-endothelial cell interactions in endothelial NOS deficient mice

Maria Jesus Sanz, Michael J. Hickey, Brent Johnston, Donna Marie McCafferty, Eko Raharjo, Paul L. Huang, Paul Kubes

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Abstract

1. The present study was designed to examine the possible role of neuronal nitric oxide synthase (nNOS) in regulation of leukocyte-endothelial cell interactions in the absence of endothelial nitric oxide synthase (eNOS), using intravital microscopy of the cremasteric microcirculation of eNOS-/- mice. 2. Baseline leukocyte rolling and adhesion revealed no differences between wild-type and eNOS-/- mice in either the cremasteric or intestinal microcirculations. 3. Superfusion with L-NAME (100 μM) caused a progressive and significant increase in leukocyte adhesion in both wild-type and eNOS-/- mice, without detecting differences between the two strains of mice. 4. Superfusion with 7-nitroindazole (100 μM), a selective inhibitor of nNOS, had no effect on leukocyte adhesion in wild-type animals. However, it increased leukocyte adhesion significantly in eNOS-/- mice, which was reversed by systemic L-arginine pre-administration. 5. Stimulation of the microvasculature with H2O2 (100 μM) induced a transient elevation in leukocyte rolling in wild-type mice. Conversely, the effect persisted during the entire 60 min of experimental protocol in eNOS-/- mice either with or without 7-nitroindazole. 6. Semi-quantitative analysis by RT - PCR of the mRNA for nNOS levels in eNOS-/- and wild-type animals, showed increased expression of nNOS in both brain and skeletal muscle of eNOS-/- mice. 7. In conclusion, we have demonstrated that leukocyte-endothelial cell interactions are predominantly modulated by eNOS isoform in postcapillary venules of normal mice, whereas nNOS appears to assume the same role in eNOS-/- mice. Interestingly, unlike eNOS there was insufficient NO produced by nNOS to overcome leukocyte recruitment elicited by oxidative stress, suggesting that nNOS cannot completely compensate for eNOS.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalBritish Journal of Pharmacology
Volume134
Issue number2
DOIs
Publication statusPublished - 1 Jan 2001
Externally publishedYes

Keywords

  • Endothelium
  • eNOS
  • Hydrogen peroxide
  • Intravital microscopy
  • Leukocyte
  • nNOS
  • NO

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