Related Experiment Videos
Nitric oxide inhibits microvascular protein leakage induced by leukocyte adhesion-independent and adhesion-dependent
B Johnston1, J P Gaboury, M Suematsu
1Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
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.
Insights
Exogenous nitric oxide (NO) and 8-Br-cGMP can block inflammatory mediator-induced vascular permeability. NO is effective against both histamine and CINC/gro, while 8-Br-cGMP primarily affects CINC/gro-induced changes.
Area of Science:
- Physiology
- Pharmacology
- Inflammation Research
Background:
- Vascular permeability is modulated by inflammatory mediators.
- Nitric oxide (NO) plays a role in regulating vascular responses.
- Understanding NO's role in different inflammatory pathways is crucial.
Purpose of the Study:
- To investigate if exogenous nitric oxide (NO) can prevent permeability changes caused by histamine and CINC/gro.
- To differentiate the effects of NO and 8-Br-cGMP on mediator-induced vascular leakage.
Main Methods:
- Intravital microscopy in rat mesentery.
- Assessment of leukocyte adhesion and FITC-albumin leakage.
- Evaluation of mast cell activation and effects of spermine-NO and 8-Br-cGMP.
Main Results:
- Histamine increased protein leakage, preventable by spermine-NO but not 8-Br-cGMP.
- CINC/gro increased leukocyte adhesion and protein leakage, attenuated by both spermine-NO and 8-Br-cGMP.
- Neither mediator activated mast cells, ruling out mast cell stabilization.
Conclusions:
- Exogenous NO and 8-Br-cGMP block CINC/gro-induced, adhesion-dependent permeability.
- Exogenous NO blocks histamine-induced, adhesion-independent permeability, but 8-Br-cGMP does not.
- Distinct NO-dependent signaling pathways likely modulate different types of vascular protein leakage.