scholarly journals Inorganic nitrate attenuates cardiac dysfunction: role for xanthine oxidoreductase and nitric oxide

2021 ◽  
Author(s):  
Lorna C. Gee ◽  
Gianmichele Massimo ◽  
Clement Lau ◽  
Christopher Primus ◽  
Daniel Fernandes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Dysfunction ◽  
Xanthine Oxidoreductase ◽  
Inorganic Nitrate

Abstract 111: Xanthine Oxidoreductase Plays a Key Role in Nitrate, Nitrite and Nitric Oxide Homeostasis When the Endothelial Nitric Oxide Synthase is Compromised

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Christa Zollbrecht ◽  
Marcelo Montenegro ◽  
Michael Hezel ◽  
Eddie Weitzberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Primary Source ◽  
No Production ◽  
Xanthine Oxidoreductase ◽  
Physiological Conditions ◽  
Inorganic Nitrate ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Xanthine oxidoreductase (XOR) is generally known as a source of superoxide production, but this enzyme has also been suggested to mediate NO production via reduction of inorganic nitrate (NO 3 - ) and nitrite(NO 2 - ). This pathway for NO generation is of particular importance during certain pathologies, whereas endothelial NO synthase (eNOS) is the primary source of vascular NO generation under normal physiological conditions. The exact interplay between the NOS and XOR-derived NO is not yet fully elucidated. The aim of the present study was to investigate if eNOS deficiency is partly compensated by XOR upregulation and sensitization of the NO 3 - - NO 2 - - NO pathway. NO 3 - and NO 2 - were similar between naïve eNOS KO and wildtype (wt) mice, but reduced upon chronic treatment with the non-selective NOS inhibitor L-NAME (wt: 25.0±5.2, eNOS KO: 39.2±6.4, L-NAME: 8.2±1.6 μ NO 3 - -, wt: 0.38±0.07, eNOS KO: 0.42±0.04, L-NAME: 0.12±0.02 μ NO 2 - ). XOR function was upregulated in eNOS KO compared with wt mice [(mRNA: wt 1±0.07, eNOS KO 1.38±0.17), (activity: wt 825±54, eNOS KO 1327±280 CLU/mg/min), (uric acid: wt 32.87±1.53, eNOS KO 43.23±3.54 μ)]. None of these markers of XOR activity was increased in nNOS KO and iNOS KO mice. Following acute dose of NO 3 - (10 mg/kg bw, i.p.), the increase of plasma NO 2 - was more pronounced in eNOS KO (+0.51±0.13 μ) compared with wt (+0.22±0.09 μ), and this augmented response in the eNOS KO was abolished by treatment with the highly selective XOR inhibitor febuxostat (FEB). Liver from eNOS KO had higher reducing capacity of NO 2 - to NO compared with wt, and this effect was attenuated by FEB (Δppb of NO: wt +8.7±4.2, eNOS KO +44.2±15.0, wt+FEB +22.2±9.6, eNOS KO+FEB +26.8±10.2). Treatment with FEB increased blood pressure in eNOS KO (ΔMAP:+10.2±5.6 mmHg), but had no effect in wt (ΔMAP:-0.6±3.3 mmHg). Supplementation with NO 3 - (10 mM, drinking water) reduced blood pressure in eNOS KO (ΔMAP: -6.3±2.2 mmHg), and this effect was abolished by FEB (ΔMAP: +1.1±1.9 mmHg). In conclusion, upregulated and altered XOR function in conditions with eNOS deficiency can facilitate the NO 3 - - NO 2 - - NO pathway and hence play a significant role in vascular NO homeostasis.

Suicide inactivation of xanthine oxidoreductase during reduction of inorganic nitrite to nitric oxide

2001 ◽  
Vol 358 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Ben L. J. GODBER ◽  
Justin J. DOEL ◽  
Tracey A. GOULT ◽  
Robert EISENTHAL ◽  
Roger HARRISON
Keyword(s):  
Nitric Oxide ◽  
Kinetic Model ◽  
Nitrite Reduction ◽  
Stoichiometric Ratio ◽  
Enzyme Complex ◽  
Xanthine Oxidoreductase ◽  
Nitrite Concentration ◽  
Enzyme Substrate ◽  
Inorganic Nitrate ◽  
Suicide Inactivation

Xanthine oxidoreductase (XOR) is progressively inactivated while catalysing the reduction of inorganic nitrite to NO by xanthine. Inactivation results from conversion of the enzyme into its desulpho-form. The rate of inactivation increases with nitrite concentration. Similar behaviour was shown when NADH replaced xanthine as reducing substrate. A kinetic model is proposed incorporating a ‘suicide’ inactivation involving an enzyme–substrate (product) complex, rather than inactivation by free NO. The model provides a good fit to progress curves of the reaction of xanthine or NADH with nitrite in the presence of the oxidase or dehydrogenase forms of the enzyme. Inorganic nitrate, like nitrite, was shown to be reduced at the molybdenum site of XOR. With xanthine as reducing substrate, nitrite was produced in essentially a 1:1 stoichiometric ratio with respect to urate. Unlike the case of nitrite, the enzyme was not significantly inactivated, implying that inactivation during nitrite reduction depends on the presence of nascent NO in its enzyme complex.

scholarly journals Nitric oxide and hypoxia at adaptation to muscular work (brief review)

2016 ◽  
Vol 14 (1) ◽  
pp. 78-88
Author(s):  
Alexander S Radchenko
Keyword(s):  
Nitric Oxide ◽  
Performance Improvement ◽  
Healthy Person ◽  
The Body ◽  
Hypoxic Exposure ◽  
Muscular Work ◽  
Muscle Work ◽  
Inorganic Nitrate ◽  
Mechanisms Of Adaptation ◽  
Nitrate Supplementation

The The last two decades there has been a growing interest in the nitric oxide (NO) function in the body of a healthy person. In the study, two very specific problems are discussed: a) the NO involvement in mechanisms of adaptation at muscular work under hypoxia conditions, and b) the inorganic nitrate supplementation in athlete’s diet with the aim of sports performance improvement. The reorganizations that occur in the heart vasculature and in skeletal muscle for providing muscle work under hypoxia conditions examined. The named problems are particularly relevant in contemporary sports in which the adding of hypoxic exposure on a body of training persons as well as the inorganic nitrate in sports nutrition application as added means to special performance improvement. Raise the problem of the hypoxia and inorganic nitrate mutual exploitation in the training process.

A nitric oxide‐releasing derivative of enalapril, NCX 899, prevents progressive cardiac dysfunction and remodeling in hamsters with heart failure

2004 ◽  
Vol 18 (3) ◽  
pp. 587-588 ◽  
Author(s):  
Yoshitaka Iwanaga ◽  
Yusu Gu ◽  
Thomas Dieterle ◽  
Cristina Presotto ◽  
Piero Del Soldato ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Nitric Oxide Releasing

Significance of Inorganic Nitrate Supplement in Cardiovascular Health

2021 ◽  
Vol 19 ◽  
Author(s):  
Rupesh Dudhe ◽  
Anshu Chaudhary Dudhe ◽  
Shravan D. Raut
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Health ◽  
Substantial Reduction ◽  
General Information ◽  
Pressure Limit ◽  
Inorganic Nitrate ◽  
Nitrate Supplementation ◽  
Sequential Reduction ◽  
Oxide Synthase ◽  
Progression Of Atherosclerosis

Background amp; Objectives: Nitric Oxide (NO) is frequently produced by the enzyme Nitric Oxide Synthase (NOS) and is crucial to the control and effective ness of the cardiovascular system. However, there is substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular obstacles. Fortunately, NO can also being produced by sequential reduction of inorganic nitrates supplementation. This proves that NO from inorganic nitrate supplements can provide compensation when NOS activity is inadequate and cardio protective benefits and beyond that provided by healthy NOS system. Discussion: This review focus on the general information about Nitrous oxide, types, mechanism of action of NO & overview of NOS activity is inadequate and cardio protective benefits and beyond that provided by healthy NOS system were often studied for cardiovascular treatments. Conclusion: We concluded that the Natural plant NO is the essential for cardiovascular activity to target site with desired concentration. Moreover, the researchers were focused on Evidence suggested that nitrate supplementation can help regulate blood pressure, limit progression of atherosclerosis, and improve myocardial contractility in both healthy individuals and those with cardiovascular disease.

scholarly journals Nitrite-mediated reduction of macrophage NADPH oxidase activity is dependent on xanthine oxidoreductase-derived nitric oxide but independent of S-nitrosation

Redox Biology ◽  
2016 ◽  
Vol 10 ◽  
pp. 119-127 ◽  
Author(s):  
Christa Zollbrecht ◽  
A. Erik G. Persson ◽  
Jon O. Lundberg ◽  
Eddie Weitzberg ◽  
Mattias Carlström
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Xanthine Oxidoreductase ◽  
Nadph Oxidase Activity ◽  
Mediated Reduction

scholarly journals Nitric oxide and renal and cardiac dysfunction in cirrhosis

2002 ◽  
Vol 102 (2) ◽  
pp. 213 ◽  
Author(s):  
Joaquín GARCÍA-ESTAÑ ◽  
M. Clara ORTIZ ◽  
Samuel S. LEE
Keyword(s):  
Nitric Oxide ◽  
Cardiac Dysfunction

Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions

FEBS Letters ◽  
1998 ◽  
Vol 427 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Timothy M Millar ◽  
Cliff R Stevens ◽  
Nigel Benjamin ◽  
Robert Eisenthal ◽  
Roger Harrison ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Xanthine Oxidoreductase ◽  
Hypoxic Conditions
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