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Editorial
. 2015 May 19;131(20):1741-4.
doi: 10.1161/CIRCULATIONAHA.115.016379. Epub 2015 Apr 14.

Xanthine oxidase inhibitors in heart failure: where do we go from here?

Leonardo Tamariz  1 , Joshua M Hare  2
Affiliations
Editorial

Xanthine oxidase inhibitors in heart failure: where do we go from here?

Leonardo Tamariz et al. Circulation. .
No abstract available

Keywords: Editorials; antagonists and inhibitors; heart failure; nitric oxide; uric acid; xanthine oxidase.

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Figures

Figure 1
Figure 1
Effect of XO inhibition on the nitroso-redox balance. The underlying mechanistic basis for the use of xanthine oxidase inhibitors in the failing heart. As depicted xanthine oxidase inhibitors (XOI) act on one key enzyme – XO/XDH – to inhibit ROS production but has other actions that might detract from full restoration of nitroso-redox balance. XOI decrease serum uric acid and superoxide production by inhibiting xanthine oxidase. Importantly, however, there are other sources of ROS production in the failing heart, including mitochonrdrial respiration and NADPH oxidases, that are not affected by XOI. In addition, NOS activity may be impaired in heart failure, or further disrupted by XOI. In states of inadequate NO production, oxidation or diminished S-nitrosylation of the RYR receptor and other key proteins involved in excitation-contraction coupling impairs calcium cycling which drives optimal myocardial performance. Persistent ROS production also consumes NO and leads to peroxynitrite formation which can cause DNA, protein and lipid damage. Peroxynitrite oxidizes the calcium ATPase SERCA (responsible for calcium reuptake into the SR). Thus, NO continues to be depleted by XO inhibition perpetuating nitroso-redox imbalance and causing ineffective excitation-contraction coupling. Abbreviations: XOR: xanthine oxidoreductase, XO: xanthine oxidase, XDH: xanthine dehydrogenase, O−: Superoxide, NO: nitric oxide, NADPH: nicotine adenine dinucleotide phosphate, NOX: NADPH oxidases, 2NOS: nitric oxide synthase, SOD: superoxide dismutase, SR: sarcoplasmic reticulum, SERCA: sarcoplasmic reticulum calcium ATPase, RyR: ryanodine receptor.
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References

    1. Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385:812–824. - PubMed
    1. Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med. 2004;351:2112–2114. - PubMed
    1. Cappola TP, Kass DA, Nelson GS, Berger RD, Rosas GO, Kobeissi ZA, Marban E, Hare JM. Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy. Circulation. 2001;104:2407–2411. - PubMed
    1. Tsukimori K, Yoshitomi T, Morokuma S, Fukushima K, Wake N. Serum uric acid levels correlate with plasma hydrogen peroxide and protein carbonyl levels in preeclampsia. Am J Hypertens. 2008;21:1343–1346. - PubMed
    1. Anker SD, Doehner W, Rauchhaus M, Sharma R, Francis D, Knosalla C, Davos CH, Cicoira M, Shamim W, Kemp M, Segal R, Osterziel KJ, Leyva F, Hetzer R, Ponikowski P, Coats AJ. Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation. 2003;107:1991–1997. - PubMed

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