Nitric oxide inhibits microvascular protein leakage induced by leukocyte adhesion-independent and adhesion-dependent inflammatory mediators

Brent Johnston, Jeffrey P. Gaboury, Makoto Suematsu, Paul Kubes

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective: The purpose of this study was to determine whether exogenous nitric oxide could block permeability alterations induced by neutrophil-independent (histamine) and neutrophil-dependent (CINC/gro) inflammatory mediators. Methods: Intravital microscopy was used in the rat mesentery to examine leukocyte adhesion, transvascular FITC-albumin leakage, and perivascular mast cell activation (ruthenium red uptake) in response to local superfusion with histamine or the chemokine CINC/gro. The effects of the nitric oxide donor spermine-NO, or the cGMP analog 8-Br-cGMP were examined. Results: Histamine superfusion increased vascular protein leakage within minutes, but did not increase firm adhesion above that seen in control preparations. The increase in albumin leakage could be prevented by co-administration of spermine-NO, but was not affected by 8-Br-cGMP. CINC/gro elicited a linear increase in vascular protein leakage and a profound increase in leukocyte adhesion. Treatment with spermine-NO or 8-Br-cGMP significantly attenuated increases in both adhesion and albumin leakage. The actions of spermine-NO and 8-Br-cGMP were not due to mast cell stabilization as neither histamine nor CINC/gro elicited mast cell activation. Conclusions: This study demonstrates that exogenous nitric oxide and 8-Br-cGMP could block adhesion dependent alterations in vascular permeability induced by CINC/gro, while adhesion-independent alterations in permeability induced by histamine could be blocked by exogenous NO but not 8-Br-cGMP. This suggests that different NO-dependent signalling pathways are important in modulating these two types of vascular protein leakage.

Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalMicrocirculation
Volume6
Issue number2
DOIs
Publication statusPublished - 1999 Jan 1

Keywords

  • Chemokine
  • Histamine
  • Intravital microscopy
  • Leukocyte adhesion
  • Mast cell
  • Nitric oxide
  • Rolling
  • Vascular permeability
  • Venule
  • cGMP

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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