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Peroxynitrite does not impair pulmonary and systemic vascular responses.
B D Nossaman1, P A Dabisch, J T Liles
1Department of Anesthesiology, Tulane University Health Science Center, New Orleans, Louisiana 70112, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|January 13, 2004
Summary
Peroxynitrite (ONOO-) significantly impacts vascular tone, causing vasodilation in some areas and vasoconstriction in others. Its effects are rapid and repeatable, independent of cyclooxygenase pathways.
Area of Science:
- Cardiovascular Physiology
- Vascular Pharmacology
- Reactive Nitrogen Species Biology
Background:
- Peroxynitrite (ONOO-) is a reactive nitrogen species implicated in various physiological and pathological processes.
- Understanding ONOO-'s role in vascular regulation is crucial for cardiovascular health.
- Previous studies suggest complex interactions between ONOO- and vascular tone.
Purpose of the Study:
- To investigate the effects of peroxynitrite (ONOO-) on systemic, hindquarters, and pulmonary vascular beds.
- To determine the dose-dependency, onset, duration, and repeatability of ONOO- vascular responses.
- To elucidate the mechanisms underlying ONOO-'s vascular actions, including potential cyclooxygenase involvement.
Main Methods:
- Administered intravenous ONOO- injections in rats to assess systemic arterial pressure.
- Infused ONOO- into the hindquarters vascular bed and rat lung perfusion circuit to measure perfusion pressures.
- Evaluated the impact of repeated ONOO- exposure on responses to vasodilators, vasoactive agonists, and hypoxic pulmonary vasoconstriction.
- Tested the effects of sodium nitrate, nitrite, and decomposed ONOO-.
- Utilized a cyclooxygenase inhibitor to assess its influence on ONOO- mediated responses.
Main Results:
- ONOO- injections decreased systemic arterial pressure and hindquarters perfusion pressure in a dose-dependent manner.
- ONOO- administration increased pulmonary arterial perfusion pressure in the isolated perfused rat lung.
- Vascular responses to ONOO- were rapid, short-lived, and repeatable without tachyphylaxis.
- Repeated ONOO- exposure did not alter responses to endothelium-dependent vasodilators or other vasoactive agents.
- ONOO- effects were independent of cyclooxygenase activity and hypoxic pulmonary vasoconstriction.
Conclusions:
- Peroxynitrite exhibits potent pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activities.
- Short-term, repeated exposure to ONOO- can modulate vascular responsiveness.
- The vascular actions of ONOO- are not mediated by cyclooxygenase products.