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NO generation from nitrite and its role in vascular control
Jon O Lundberg1, Eddie Weitzberg
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. jon.lundberg@fyfa.ki.se
Arteriosclerosis, Thrombosis, and Vascular Biology
|March 5, 2005
Summary
Nitrite and nitrate, once thought inert, can be recycled to bioactive nitric oxide (NO). This pathway offers a backup NO source, challenging previous understandings of NO metabolism and vascular control.
Area of Science:
- Physiology
- Biochemistry
- Vascular Biology
Background:
- Nitric oxide (NO) generated from L-arginine by NO synthases (NOSs) is crucial for vascular biology.
- NO's activity is terminated by oxidation to nitrite and nitrate, traditionally viewed as inert end-products.
- Recent findings challenge this dogma, revealing nitrite can be reduced back to bioactive NO.
Purpose of the Study:
- To discuss novel aspects of nitrite-dependent NO generation in vivo.
- To explore the role of nitrite as a potential NO storage pool.
- To examine the implications for vascular control and NO backup systems.
Main Methods:
- Literature review of recent research on nitrite metabolism and NO generation.
- Discussion of various nitrite reduction pathways (enzymatic, protein-mediated, vitamin-dependent, proton-driven).
- Analysis of the physiological relevance in conditions like hypoxia.
Main Results:
- Nitrite is not an inert end-product but can be recycled to bioactive NO.
- This recycling occurs through multiple biochemical routes in blood and tissues.
- Nitrite-dependent NO generation can act as a backup system when NOS/L-arginine pathways are compromised.
Conclusions:
- Nitrate and nitrite should be considered storage pools for NO.
- Nitrite-dependent NO generation has significant implications for vascular control.
- This pathway may be critical in physiological and pathophysiological states, including hypoxia.