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Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

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Cardiovascular effects of peroxynitrite.

Rao M Uppu¹, Bobby D Nossaman, Anthony J Greco

¹Department of Environmental Toxicology and the Health Research Center, Southern University and A&M College, Baton Rouge, LA, USA.

Clinical and Experimental Pharmacology & Physiology

|July 25, 2007

Summary

Peroxynitrite (PN), formed from nitric oxide and superoxide, generates beneficial NO-donor substances via CO2 reactions. These products protect against tissue injury and improve cardiovascular function.

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Area of Science:

Biochemistry
Physiology
Oxidative Stress

Background:

Peroxynitrite (PN) is synthesized from nitric oxide (NO) and superoxide (O2(-)*).
PN itself is not a free radical but can generate nitrogen dioxide (NO2) and carbonate radical (CO3(-)*) when reacting with CO2.
CO2 is abundant in biological fluids, making its reaction with PN a significant metabolic pathway.

Purpose of the Study:

To review the chemistry of peroxynitrite.
To explore how PN effects are mediated by NO-donor substance formation.
To discuss the physiological and beneficial impacts of PN.

Main Methods:

Literature review of peroxynitrite chemistry and biological effects.
Analysis of reaction pathways involving PN, CO2, and biological molecules.
Evaluation of evidence for NO-donor formation from PN reactions.

Main Results:

PN reacts rapidly with CO2, a major pathway for its disposition in vivo.
Generated radicals (NO2, CO3(-)*) can cause oxidative damage.
Reactions of PN-derived species with biomolecules yield nitration and nitrosation products.
These products act as long-acting NO donors, conferring vasorelaxant and cardioprotective effects.
Beneficial effects include reduced inflammation and protection against reperfusion injury.

Conclusions:

PN metabolism via CO2 is crucial in biological systems.
PN-derived NO donors contribute significantly to beneficial physiological outcomes.
Understanding PN chemistry is key to appreciating its dual role in health and disease.