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Published on: December 23, 2014
Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema
1Research Service, Samuel S. Stratton Veterans Affairs Medical Center, Albany, New York, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|June 1, 1996
Summary
Nitrovasodilator repletion worsens tumor necrosis factor-alpha (TNF-alpha) induced pulmonary edema. This effect may be mediated by peroxynitrite (ONOO-), suggesting new therapeutic targets for lung injury.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Vascular Biology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine implicated in various lung pathologies.
- Pulmonary edema, characterized by fluid accumulation in the lungs, is a serious complication of inflammatory conditions.
- The role of nitric oxide (NO) and its derivatives in TNF-alpha-induced lung injury requires further elucidation.
Purpose of the Study:
- To investigate whether augmenting nitric oxide (NO) availability exacerbates TNF-alpha-induced pulmonary edema.
- To explore the potential involvement of peroxynitrite (ONOO-) in this inflammatory process.
Main Methods:
- Isolated guinea pig lungs were perfused under control conditions or after TNF-alpha administration.
- Pulmonary capillary pressure (Ppc) and lung weight changes (delta W) were measured.
- The effects of a nitrovasodilator agonist (SNAP) and a peroxynitrite scavenger (urate) were assessed.
Main Results:
- In TNF-alpha treated lungs, SNAP failed to attenuate vasoconstriction but increased lung weight, indicating edema.
- The peroxynitrite scavenger urate abolished the edema formation in TNF-alpha + SNAP treated lungs.
- Exogenous peroxynitrite (ONOO-) administration enhanced edema formation.
Conclusions:
- Nitric oxide repletion potentiates TNF-alpha-induced pulmonary edema.
- Peroxynitrite (ONOO-) appears to be a critical mediator in this process.
- Targeting peroxynitrite formation may offer a therapeutic strategy for TNF-alpha-mediated lung injury.
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