C. Duncan

Bio: C. Duncan is an academic researcher from University of Aberdeen. The author has contributed to research in topics: Nitrite & Nitrate. The author has an hindex of 7, co-authored 11 publications receiving 2170 citations. Previous affiliations of C. Duncan include Rowett Research Institute.

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

Abstract: High concentrations of nitrite present in saliva (derived from dietary nitrate) may, upon acidification, generate nitrogen oxides in the stomach in sufficient amounts to provide protection from swallowed pathogens. We now show that, in the rat, reduction of nitrate to nitrite is confined to a specialized area on the posterior surface of the tongue, which is heavily colonized by bacteria, and that nitrate reduction is absent in germ-free rats. We also show that in humans increased salivary nitrite production resulting from nitrate intake enhances oral nitric oxide production. We propose that the salivary generation of nitrite is accomplished by a symbiotic relationship involving nitrate-reducing bacteria on the tongue surface, which is designed to provide host defence against microbial pathogens in the mouth and lower gut. These results provide further evidence for beneficial effects of dietary nitrate.

Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans.

Abstract: BACKGROUND/AIMS: It has been suggested that dietary nitrate, after concentration in the saliva and reduction to nitrite by tongue surface bacteria, is chemically reduced to nitric oxide (NO) in the acidic conditions of the stomach. This study aimed to quantify this in humans. METHODS: Ten healthy fasting volunteers were studied twice, after oral administration of 2 mmol of potassium nitrate or potassium chloride. Plasma, salivary and gastric nitrate, salivary and gastric nitrite, and gastric headspace NO concentrations were measured over six hours. RESULTS: On the control day the parameters measured varied little from basal values. Gastric nitrate concentration was 105.3 (13) mumol/l (mean (SEM), plasma nitrate concentration was 17.9 (2.4) mumol/l, salivary nitrate concentration 92.6 (31.6) mumol/l, and nitrite concentration 53.9 (22.8) mumol/l. Gastric nitrite concentrations were minimal (< 1 mumol/l). Gastric headspace gas NO concentration was 16.4 (5.8) parts per million (ppm). After nitrate ingestion, gastric nitrate peaked at 20 minutes at 3430 (832) mumol/l, plasma nitrate at 134 (7.2) mumol/l, salivary nitrate at 1516.7 (280.5) mumol/l, and salivary nitrite at 761.5 (187.7) mumol/l after 20-40 minutes. Gastric nitrite concentrations tended to be low, variable, and any rise was non-sustained. Gastric NO concentrations rose considerably from 14.8 (3.1) ppm to 89.4 (28.6) ppm (p < 0.0001) after 60 minutes. All parameters remained increased significantly for the duration of the study. CONCLUSIONS: A very large and sustained increase in chemically derived gastric NO concentrations after an oral nitrate load was shown, which may be important both in host defence against swallowed pathogens and in gastric physiology.

Dietary nitrate in man: friend or foe?

Abstract: Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.

The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics

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

Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite

Abstract: Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Delta(max) -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease.

Nitrate in vegetables: toxicity, content, intake and EC regulation

Abstract: Nitrate content is an important quality characteristic of vegetables. Vegetable nitrate content is of interest to governments and regulators owing to the possible implications for health and to check that controls on the content are effective. Nitrate itself is relatively non-toxic but its metabolites may produce a number of health effects. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Recent research studies suggest that nitrate is actually a key part of our bodies' defences against gastroenteritis. In this review are reported: (1) vegetable classification as a function of nitrate accumulation; (2) vegetable contribution to the total dietary exposure of nitrate; (3) European Commission Regulation No. 563/2002 which sets limits for nitrate in lettuce and spinach; (4) the maximum levels set in some countries for beetroot, cabbage, carrot, celery, endive, Lamb's lettuce, potato, radish and rocket; (5) the results of surveys on the nitrate content of vegetables in Italy and other European countries.  2005 Society of Chemical Industry

Exhaled markers of pulmonary disease.

Abstract: Introduction Nitric Oxide Source of NO in exhaled air Measurement Asthma COPD Cystic fibrosis Bronchiectasis Primary ciliary dyskinesia Rhinitis Interstitial lung diseases Pulmonary hypertension Occupational diseases Infections Chronic cough Lung cancer Lung transplant rejection Adult respiratory distress syndrome Diffuse Panbronchiolitis Carbon Monoxide Source of exhaled CO Measurement Asthma COPD Bronchiectasis Cystic fibrosis Interstitial lung disease Allergic rhinitis Infections Other conditions Exhaled Hydrocarbons Origin Measurement Asthma COPD Cystic Fibrosis Other lung diseases Exhaled Breath Condensate Origin Hydrogen peroxide Eicosanoids Products of lipid peroxidation Vasoactive amines NO-related products Ammonia Electrolytes Hydrogen ions Proteins and cytokines Other Methods Exhaled temperature Combined gas chromatography/spectroscopy The selected ion flow tube (SIFT) technique Polymer-coated surface-acoustic-wave resonators Future Directions Standardization of measurements Clinical application Profiles of mediators Measuring devices New markers