9/12/2016 Lundberg 

JO, Weitzberg E, Gladwin MTThe nitrate­nitrite­nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7:156­167

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881 Citations 154 References

Lundberg JO, Weitzberg E, Gladwin

MTThe nitrate-nitrite-nitric oxide
pathway in physiology and therapeutics.
Nat Rev Drug Discov 7:156-167
Article in Nature Reviews Drug Discovery 7(2):156-67 · March 2008 with 123 Reads
DOI: 10.1038/nrd2466 · Source: PubMed

1st Jon O Lundberg 2nd Eddie Weitzberg

3rd Mark T Gladwin

Abstract
The inorganic anions nitrate (NO3-) and nitrite (NO2-) were previously thought to be inert
end products of endogenous nitric oxide (NO) metabolism. However, recent studies show
that these supposedly inert anions can be recycled in vivo to form NO, representing an
important alternative source of NO to the classical L-arginine-NO-synthase pathway, in
particular in hypoxic states. This Review discusses the emerging important biological
functions of the nitrate-nitrite-NO pathway, and highlights studies that implicate the
therapeutic potential of nitrate and nitrite in conditions such as myocardial infarction,
stroke, systemic and pulmonary hypertension, and gastric ulceration.

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Citations 881 References 154

Recent advances in the chemical biology of nitroxyl (HNO) detection and

generation

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9/12/2016 Lundberg JO, Weitzberg E, Gladwin MTThe nitrate­nitrite­nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7:156­167

"Overall, these results provide a unique potential endogenous

pathway for the conversion of NO to HNO in the presence of
these " reducing " alcohols and theoretically make any NO
source a source of HNO. Given the numerous systems
capable of reducing nitrite (NO À 2 ) to NO and the known
conversion of dietary nitrate to nitrite by oral bacteria in
humans and the subsequent chemical or enzymatic
reduction of nitrite to NO, a large number of potential
endogenous HNO generating systems appear possible [155].
"

[Show abstract]

Full-text · Article · Apr 2016

Zhengrui Miao S Bruce King

Read full-text

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic

Approaches

") [293] . Thus, dietary administration of nitrate has revealed

a new therapeutic perspective. "

[Show abstract]

Article · Jun 2015

Dimitris Tousoulis Marios K Georgakis Evangelos Oikonomou

+4 more authors ... Gerasimos Siasos

Read

Effects of long-term dietary nitrate supplementation in mice

"After the discovery of nitric oxide (NO) as a biological

signaling molecule nitrate and nitrite have been used as
stable surrogate markers of NO synthase-derived NO [3].
More recently an alternative pathway of NO generation was
described in which serial reduction of nitrate and nitrite to
NO and other bioactive nitrogen intermediates occurs [4].
This NO synthase (NOS) independent pathway relies on
retention of nitrate anions through salivary concentration
from the plasma. "

[Show abstract]

Full-text · Article · May 2015

Michael P. Hezel Ming Liu Tomas A. Schiffer +5 more authors ...

Eddie Weitzberg

Read full-text

Show more

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9/12/2016 Lundberg JO, Weitzberg E, Gladwin MTThe nitrate­nitrite­nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7:156­167

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