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Peroxynitrite: a mediator of increased microvascular permeability?
S Greenacre1, V Ridger, P Wilsoncroft
1Pharmacology Group, King's College, London, United Kingdom.
Clinical and Experimental Pharmacology & Physiology
|November 18, 1997
Summary
Peroxynitrite, a product of inflammation, causes swelling by increasing microvascular permeability in rat skin. This finding suggests peroxynitrite plays a role in inflammatory processes beyond its direct cell damage.
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are elevated at inflammatory sites.
- Peroxynitrite, formed from superoxide and NO, is implicated in pro-inflammatory processes.
- The role of peroxynitrite in inducing edema formation requires investigation.
Purpose of the Study:
- To investigate the ability of peroxynitrite to induce edema formation in rat cutaneous microvasculature.
- To determine if peroxynitrite directly increases microvascular permeability.
- To assess the pro-inflammatory potential of peroxynitrite.
Main Methods:
- Peroxynitrite synthesized from hydrogen peroxide and acidified nitrite.
- Spectrophotometry used for peroxynitrite concentration and breakdown measurement.
- Edema measured by [125I]-albumin extravasation in rat skin after intradermal injection.
Main Results:
- Peroxynitrite induced dose-dependent edema formation (24-69 µL increase in plasma extravasation).
- Significantly greater plasma extravasation observed with 100 and 200 nmol peroxynitrite compared to controls.
- Edema was a direct microvascular response to peroxynitrite, not due to pH or contaminants.
Conclusions:
- Peroxynitrite increases microvascular permeability and induces edema formation.
- Peroxynitrite may mediate vascular pro-inflammatory effects.
- Peroxynitrite's role in inflammation extends beyond direct cytotoxic activity.