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Platelet activating factor-induced microvascular permeability increases in the cat hindlimb
1Department of Physiology, University of South Carolina School of Medicine, Columbia 29208.
Circulatory Shock
|September 1, 1993
Summary
Platelet-activating factor (PAF) increases microvascular permeability more potently than histamine. While both mediators cause endothelial contraction, their pathways differ, and high concentrations lead to sustained permeability increases resistant to inhibition.
Area of Science:
- Pharmacology
- Physiology
- Microcirculation
Background:
- Platelet-activating factor (PAF) and histamine are key inflammatory mediators.
- Understanding their distinct roles in microvascular permeability is crucial for treating inflammatory conditions.
Purpose of the Study:
- To compare the effects of PAF and histamine on microvascular permeability in a perfused cat hindlimb model.
- To investigate the specific pathways and receptor involvement in mediator-induced permeability changes.
Main Methods:
- Isolated, perfused cat hindlimb preparation.
- Measurement of microvascular permeability via protein reflection coefficient, hematocrit, and protein concentration changes.
- Utilized specific receptor blockers (WEB-2086, Diphenhydramine, Cimetidine) and a beta-agonist (Isoproterenol).
Main Results:
- PAF is ~30 times more potent than histamine in increasing permeability.
- PAF-induced permeability is partially inhibited by WEB-2086 at maximal doses, unlike histamine's H1-receptor mediated effects.
- Isoproterenol inhibited histamine but not PAF effects.
- PAF's effects were independent of white blood cells.
Conclusions:
- PAF and histamine increase microvascular permeability through distinct pathways but converge on endothelial contraction.
- High concentrations of these mediators can cause sustained permeability increases, particularly relevant in shock states.
- Targeting specific receptors may offer differential therapeutic strategies for inflammatory responses.