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Editorial
. 2012 Jun 12;125(23):2824-6.
doi: 10.1161/CIRCULATIONAHA.112.107821. Epub 2012 May 9.

Nitrate-nitrite-nitric oxide pathway in pulmonary arterial hypertension therapeutics

Courtney E Sparacino-Watkins, Yen-Chun Lai, Mark T Gladwin
Editorial

Nitrate-nitrite-nitric oxide pathway in pulmonary arterial hypertension therapeutics

Courtney E Sparacino-Watkins et al. Circulation. .
No abstract available

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Conflict of interest statement

Conflict of interest: Dr. Gladwin is listed as a co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases. Dr. Gladwin consults with Aires Pharmaceuticals on the development of a phase II proof of concept trial using inhaled nitrite for pulmonary arterial hypertension.

Figures

Figure 1
Figure 1
Nitrite (NO2−), and nitrate (NO3−) can treat PAH via biotransformation into nitric oxide (NO), a potent vasodilator. The nitrate-nitrite-NO pathway dominates under hypoxia (blue lung), and the arginine-NO pathway under normoxia (red lung). Abbreviations: nitric oxide synthase (NOS); xanthine oxidoreductase (XO); deoxyhemoglobin (deoxyHgb); oxyhemoglobin (oxyHgb); ceruloplasmin (CP); guanosine triphosphate (GTP); cytosolic guanylate cyclase (cGC); cyclic guanosine monophosphate (cGMP).
Scheme 1
Scheme 1
Scheme 2
Scheme 2
See this image and copyright information in PMC

Comment in

Comment on

References

    1. Tabima DM, Frizzell S, Gladwin MT. Reactive oxygen and nitrogen species in pulmonary hypertension. Free Radical Biology and Medicine. 2012 - PMC - PubMed
    1. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery. 2008;7:156–167. - PubMed
    1. Zuckerbraun BS, Shiva S, Ifedigbo E, Mathier MA, Mollen KP, Rao J, Bauer PM, Choi JJW, Curtis E, Choi AMK, Gladwin MT. Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase–dependent nitric oxide generation. Circulation. 2010;121:98–109. - PubMed
    1. Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG, Gladwin MT. Inhaled nebulized nitrite is a hypoxia-sensitive no-dependent selective pulmonary vasodilator. Nat Med. 2004;10:1122–1127. - PubMed
    1. Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, Ognibene FP, Cannon RO. Role of circulating nitrite and s-nitrosohemoglobin in the regulation of regional blood flow in humans. Proceedings of the National Academy of Sciences; 2000; pp. 11482–11487. - PMC - PubMed

MeSH terms