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
Publication statusPublished - 1999

Fingerprint

Spermine
Histamine
Nitric Oxide
Leukocytes
Mast Cells
Blood Vessels
Proteins
Albumins
Permeability
Neutrophils
Ruthenium Red
Mesentery
Nitric Oxide Donors
Capillary Permeability
Chemokines

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nitric oxide inhibits microvascular protein leakage induced by leukocyte adhesion-independent and adhesion-dependent inflammatory mediators. / Johnston, Brent; Gaboury, Jeffrey P.; Suematsu, Makoto; Kubes, Paul.

In: Microcirculation, Vol. 6, No. 2, 1999, p. 153-162.

Research output: Contribution to journalArticle

Johnston, Brent ; Gaboury, Jeffrey P. ; Suematsu, Makoto ; Kubes, Paul. / Nitric oxide inhibits microvascular protein leakage induced by leukocyte adhesion-independent and adhesion-dependent inflammatory mediators. In: Microcirculation. 1999 ; Vol. 6, No. 2. pp. 153-162.
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