Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate

Duncan, Callum W.; Dougall, Hamish; Johnston, Peter; Green, Sue; Brogan, Richard; Leifert, Carlo; Smith, Lorna; Golden, Michael; Benjamin, Nigel

doi:10.1038/nm0695-546

Cited by 627 publications

(425 citation statements)

References 32 publications

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“…The production of U NO independent of the U NO synthases has been reported under conditions of gastric acidity [24,35,36], in acidified urine [37], on the skin surface [38,39] and in the oral cavity [11]. This nonenzymatic production of U NO has been attributed to the chemical reduction of nitrite in acidic environments [7,8].…”

Section: Discussionmentioning

confidence: 96%

“…In the body, nitrite derives from nutritional sources, from reduction of ingested nitrate by commensal bacteria and from oxidation of endogenous U NO [9]. Major dietary sources of nitrite include cured meat and cereals but about 90% of ingested nitrite by humans is accounted for by the reduction of nitrate (present in high content in green leafy vegetables such as lettuce and spinach) in the oral cavity via the action of nitrate reductase expressed by microorganisms present in the surface of the mouth [10][11][12]. Ingested nitrate is readily absorbed in the upper small intestine [13] and equilibrates with body fluids but 25% is actively secreted by the salivary glands back to the mouth [14].…”

Section: Introductionmentioning

confidence: 99%

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Red wine-dependent reduction of nitrite to nitric oxide in the stomach

Gago

Lundberg

Barbosa

et al. 2007

Free Radical Biology and Medicine

158

111

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Nitrite may be a source for nitric oxide ( U NO), particularly in highly acidic environments, such as the stomach. Diet products contribute also with reductants that dramatically increase the production of U NO from nitrite. Red wine has been attributed health promoting properties largely on basis of the reductive antioxidant properties of its polyphenolic fraction. We show in vitro that wine, wine anthocyanin fraction and wine catechol (caffeic acid) dose-and pH-dependently promote the formation of U NO when mixed with nitrite, as measured electrochemically. The production of U NO promoted by wine from nitrite was substantiated in vivo in healthy volunteers by measuring U NO in the air expelled from the stomach, following consumption of wine, as measured by chemiluminescence. Mechanistically, the reaction involves the univalent reduction of nitrite, as suggested by the formation of U NO and by the appearance of EPR spectra assigned to wine phenolic radicals. Ascorbic and caffeic acids cooperate in the reduction of nitrite to U NO. Moreover, reduction of nitrite is critically dependent on the phenolic structure and nitro-derivatives of phenols are also formed, as suggested by caffeic acid UV spectral modifications. The reduction of nitrite may reveal previously unrecognized physiologic effects of red wine in connection with U NO bioactivity.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Red wine-dependent reduction of nitrite to nitric oxide in the stomach

Gago

Lundberg

Barbosa

et al. 2007

Free Radical Biology and Medicine

158

111

View full text Add to dashboard Cite

show abstract

“…Instead, the benefits of nitrate supplementation appear to be related to an increased production of the multifunctional signalling molecule nitric oxide (NO). Ingested nitrate is reduced to nitrite by symbiotic bacteria residing predominantly on the dorsal surface of the tongue [12,13]. A portion of the nitrite is converted into NO in the acidic environment of the stomach [14,15], but the majority enters systemic circulation where it may be reduced to NO and other bioactive nitrogen oxides in the blood and tissue via various nitrite reductases [11].…”

Section: Introductionmentioning

confidence: 99%

Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness

et al. 2016

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Nitrate-rich beetroot juice (BRJ) increases plasma nitrite concentration, lowers the oxygen cost (V O2) of steady-state exercise and improves exercise performance in sedentary and moderately-trained, but rarely in well-trained individuals exercising at sea-level. BRJ supplementation may be more effective in a hypoxic environment, where the reduction of nitrite into nitric oxide (NO) is potentiated, such that well-trained and less well-trained individuals may derive a similar ergogenic effect.We conducted a randomised, counterbalanced, double-blind placebo controlled trial to determine the effects of BRJ on treadmill running performance in moderate normobaric hypoxia (equivalent to 2500 m altitude) in participants with a range of aerobic fitness levels. Twelve healthy males (V O2max ranging from 47.1 -76.8 ml·kg -1 ·min -1 ) ingested 138 ml concentrated BRJ (~ 15.2 mmol nitrate) or a nitrate-deplete placebo (PLA) (~ 0.2 mmol nitrate). Three hours later, participants completed steady-state moderate intensity running, and a 1500 m time-trial (TT) in a normobaric hypoxic chamber (FIO2 ~15 %). Plasma nitrite concentration was significantly greater following BRJ versus PLA 1 hour post supplementation, and remained higher in BRJ throughout the testing session (p < 0.01). Average V O2 was significantly lower (BRJ: 18.4 ± 2.0, PLA: 20.4 ± 12.6 ml·kg -1 ·min -1 ; p = 0.002), whilst arterial oxygen saturation (SaO2) was significantly greater (BRJ: 88.4 ± 2.7, PLA: 86.5 ± 3.3 %; p < 0.001) following BRJ. BRJ improved TT performance in all 12 participants by an average of 3.2 % (BRJ: 331.1 ± 45.3 vs. PL: 341.9 ± 46.1 s; p < 0.001). There was no apparent relationship between aerobic fitness and the improvement in performance following BRJ (r 2 = 0.05, p > 0.05). These findings suggests that a high nitrate dose in the form of a BRJ supplement may improve running performance in individuals with a range of aerobic fitness levels conducting moderate and high-intensity exercise in a normobaric hypoxic environment.

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“…88 NO has also been reported to be generated in biological systems by a non-enzymatic pathway, which involves chemical reduction of inorganic nitrite. 93 Nonenzymatic NO generation has been demonstrated in vivo, for example, in the mouth, 94 stomach, 95 on the surface of the skin, 96 in the ischemic heart, 87 in infected nitritecontaining urine 97 as well as under certain conditions involving NOS inhibitors and substrates.…”

Section: D Mapping Of Myocardial Oxygenation In the Ischemic Heartmentioning

confidence: 99%

Cardiac applications of EPR imaging

Kuppusamy

Zweíer

2004

NMR in Biomedicine

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This review summarizes the development and application of a variety of EPR imaging modalities including spatial, spectral-spatial (spectroscopic), gated-imaging and oxygen mapping to cardiovascular studies. It has been hypothesized that free radical metabolism, oxygenation and nitric oxide generation in biological organs such as the heart may vary over the spatially defined tissue structure. We have developed instrumentation optimized for 3D spatial and 3D or 4D spectral-spatial imaging of free radicals at 1.2 GHz. Using this instrumentation high quality 3D spectral-spatial imaging of nitroxyl (nitroxide) metabolism was performed, as well as spatially localized measurements of oxygen concentrations, based on the oxygen-dependent line-broadening of the EPR spectrum. Both exogenously infused probes and endogenous radicals were used to obtain the images. It is demonstrated that the EPR imaging is a powerful tool which can provide unique information regarding the spatial localization of free radicals, oxygen and nitric oxide in biological organs and tissues.

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Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate

Cited by 627 publications

References 32 publications

Red wine-dependent reduction of nitrite to nitric oxide in the stomach

Red wine-dependent reduction of nitrite to nitric oxide in the stomach

Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness

Cardiac applications of EPR imaging

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