From Nitrate to Nitric Oxide

2016 ◽  
Vol 95 (13) ◽  
pp. 1452-1456 ◽  
Author(s):  
X.M. Qu ◽  
Z.F. Wu ◽  
B.X. Pang ◽  
L.Y. Jin ◽  
L.Z. Qin ◽  
...  

The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3611
Author(s):  
Rocío González-Soltero ◽  
María Bailén ◽  
Beatriz de Lucas ◽  
Maria Isabel Ramírez-Goercke ◽  
Helios Pareja-Galeano ◽  
...  

Nitrate supplementation is an effective, evidence-based dietary strategy for enhancing sports performance. The effects of dietary nitrate seem to be mediated by the ability of oral bacteria to reduce nitrate to nitrite, thus increasing the levels of nitrite in circulation that may be further reduced to nitric oxide in the body. The gut microbiota has been recently implicated in sports performance by improving muscle function through the supply of certain metabolites. In this line, skeletal muscle can also serve as a reservoir of nitrate. Here we review the bacteria of the oral cavity involved in the reduction of nitrate to nitrite and the possible changes induced by nitrite and their effect on gastrointestinal balance and gut microbiota homeostasis. The potential role of gut bacteria in the reduction of nitrate to nitrite and as a supplier of the signaling molecule nitric oxide to the blood circulation and muscles has not been explored in any great detail.


2008 ◽  
Vol 295 (4) ◽  
pp. F912-F922 ◽  
Author(s):  
Gamika A. Prathapasinghe ◽  
Yaw L. Siow ◽  
Zhibin Xu ◽  
Karmin O

Our recent study (Prathapasinghe GA, Siow YL, O K. Am J Physiol Renal Physiol 292: F1354–F1363, 2007) indicates that homocysteine (Hcy) plays a detrimental role in ischemia-reperfusion-induced renal injury. Elevation of renal Hcy concentration during ischemia-reperfusion is attributed to reduced activity of cystathionine-β-synthase (CBS) that catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of the majority of Hcy in the kidney. However, the mechanisms of impaired CBS activity in the kidney are unknown. The aim of this study was to investigate the effects of pH and nitric oxide (NO) on the CBS activity in the kidney during ischemia-reperfusion. The left kidney of a Sprague-Dawley rat was subjected to ischemia-reperfusion. The CBS activity was significantly reduced in kidneys subjected to ischemia alone (15–60 min) or subjected to ischemia followed by reperfusion for 1–24 h. The pH was markedly reduced in kidneys upon ischemia. Injection of alkaline solution into the kidney partially restored the CBS activity during ischemia. Further analysis revealed that reduction of CBS activity during reperfusion was accompanied by an elevation of NO metabolites (nitrate and nitrite) in the kidney tissue. Injection of a NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), restored the CBS activity in the kidneys subjected to ischemia-reperfusion. Treatment with PTIO could abolish ischemia-reperfusion-induced lipid peroxidation and prevent cell death in the kidney. These results suggested that metabolic acidosis during ischemia and accumulation of NO metabolites during reperfusion contributed, in part, to reduced CBS activity leading to an elevation of renal Hcy levels, which in turn, played a detrimental role in the kidney.


1999 ◽  
Vol 5 (5) ◽  
pp. 335-341 ◽  
Author(s):  
Gavin Giovannoni ◽  
N C Silver ◽  
J O'Riordan ◽  
R F Miller ◽  
S J.R. Heales ◽  
...  

Nitric oxide (•NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of .NO in the development of progressive disease we measured the .NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit: creat.urine) and neopterin (neopt: creat.urine) to creatinine ratios compared to NC subjects. (Median[25th-75th%] nit: creat.urine: NC=1183[962-1365] vs DD=1245[875-2403], AIDS=1686[1231-2531], and RA=1950[1214-2726] mmol/mol, P50.001 and median[25th-75th%] neopt: creat.urine: NC=99[76-151] vs DD=163[119-266], AIDS=972[653-1456], and RA=389[257-623] mmol/mol, P50.001). Patients with early DD and RR MS had significantly elevated nit: creat.urine compared to patients with progressive MS (nit: creat.urine: 1612[1020-2733] vs 1159[790-1641] mmol/mol, P=0.006). The nit: creat.urine and neopt: creat.urine did not correlate with clinical relapse or MRI activity. Excretion of .NO metabolites is increased in patients with early or relapsing-remitting disease. .NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.


2019 ◽  
Vol 70 (17) ◽  
pp. 4505-4520 ◽  
Author(s):  
Antoine Berger ◽  
Alexandre Boscari ◽  
Pierre Frendo ◽  
Renaud Brouquisse

AbstractInteractions between legumes and rhizobia lead to the establishment of a symbiotic relationship characterized by the formation of a new organ, the nodule, which facilitates the fixation of atmospheric nitrogen (N2) by nitrogenase through the creation of a hypoxic environment. Significant amounts of nitric oxide (NO) accumulate at different stages of nodule development, suggesting that NO performs specific signaling and/or metabolic functions during symbiosis. NO, which regulates nodule gene expression, accumulates to high levels in hypoxic nodules. NO accumulation is considered to assist energy metabolism within the hypoxic environment of the nodule via a phytoglobin–NO-mediated respiration process. NO is a potent inhibitor of the activity of nitrogenase and other plant and bacterial enzymes, acting as a developmental signal in the induction of nodule senescence. Hence, key questions concern the relative importance of the signaling and metabolic functions of NO versus its toxic action and how NO levels are regulated to be compatible with nitrogen fixation functions. This review analyses these paradoxical roles of NO at various stages of symbiosis, and highlights the role of plant phytoglobins and bacterial hemoproteins in the control of NO accumulation.


2020 ◽  
Vol 21 (20) ◽  
pp. 7538 ◽  
Author(s):  
Pamela Pignatelli ◽  
Giulia Fabietti ◽  
Annalisa Ricci ◽  
Adriano Piattelli ◽  
Maria Cristina Curia

Nitric oxide (NO), a small gaseous and multifunctional signaling molecule, is involved in the maintenance of metabolic and cardiovascular homeostasis. It is endogenously produced in the vascular endothelium by specific enzymes known as NO synthases (NOSs). Subsequently, NO is readily oxidized to nitrite and nitrate. Nitrite is also derived from exogenous inorganic nitrate (NO3) contained in meat, vegetables, and drinking water, resulting in greater plasma NO2 concentration and major reduction in systemic blood pressure (BP). The recycling process of nitrate and nitrite to NO (nitrate-nitrite-NO pathway), known as the enterosalivary cycle of nitrate, is dependent upon oral commensal nitrate-reducing bacteria of the dorsal tongue. Veillonella, Actinomyces, Haemophilus, and Neisseria are the most copious among the nitrate-reducing bacteria. The use of chlorhexidine mouthwashes and tongue cleaning can mitigate the bacterial nitrate-related BP lowering effects. Imbalances in the oral reducing microbiota have been associated with a decrease of NO, promoting endothelial dysfunction, and increased cardiovascular risk. Although there is a relationship between periodontitis and hypertension (HT), the correlation between nitrate-reducing bacteria and HT has been poorly studied. Restoring the oral flora and NO activity by probiotics may be considered a potential therapeutic strategy to treat HT.


Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 859
Author(s):  
Diego dos Santos Baião ◽  
Davi Vieira Teixeira da Silva ◽  
Vania Margaret Flosi Paschoalin

Beetroot is a remarkable vegetable, as its rich nitrate and bioactive compound contents ameliorate cardiovascular and metabolic functions by boosting nitric oxide synthesis and regulating gene expressions or modulating proteins and enzyme activities involved in these cellular processes. Dietary nitrate provides a physiological substrate for nitric oxide production, which promotes vasodilatation, increases blood flow and lowers blood pressure. A brief narrative and critical review on dietary nitrate intake effects are addressed herein by considering vegetable sources, dosage, intervention regimen and cardioprotective effects achieved in both healthy and cardiovascular-susceptible individuals. Compared to other nitrate-rich vegetables, beets were proven to be the best choice for non-drug therapy because of their sensorial characteristics and easy formulations that facilitate patient adherence for long periods, allied to bioaccessibility and consequent effectiveness. Beets were shown to be effective in raising nitrate and nitrite in biological fluids at levels capable of promoting sustained improvement in primary and advanced hemodynamic parameters.


1995 ◽  
Vol 9 (3) ◽  
pp. 244-254 ◽  
Author(s):  
P.D. Marsh

Models of dental caries (laboratory, animal, and human in situ models) vary markedly in their microbiological complexity. Laboratory models range from mono-cultures of cariogenic species providing an acidic challenge to enamel, to the development of diverse mixed cultures growing on a habitat-simulating medium in an artificial mouth or chemostat. The latter systems are of value in determining either mechanisms of action or cause-and-effect relationships-e.g., between dietary components or antimicrobial agents and the microflora. Laboratory models have also shown that the sensitivity of oral bacteria to inhibitors is markedly reduced when growing in biofilms such as dental plaque. Animal models have proved unequivocally that caries is an infectious and transmissible disease. Their use has enabled comparisons to be made of (a) the cariogenic potential of different bacterial species, (b) the role of the diet, and (c) the effects of potential anti-caries agents. It has been claimed that no caries-protective agent currently in use has failed a rodent test. In situ human models have been designed to permit the development of "natural" plaque on standardized enamel surfaces freely exposed to the human oral environment. The microflora that develops on unadulterated surfaces is similar in composition to that found at comparable sites on vital teeth. Demineralization can be accelerated by the inoculation of additional cariogenic bacteria coupled with either intra- or extra-oral sucrose rinses. The increased realism associated with the transition from laboratory to human in situ models is countered by a reduced ability to control or manipulate the system for experimental purposes. Thus, a hierarchy of tests is needed for the study of anti-caries agents, each requiring a varying degree of microbiological complexity.


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