Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction

Xia, Dengsheng; Deng, Dajun; Wang, Songlin

doi:10.1034/j.1600-0714.2003.00109.x

Cited by 24 publications

(18 citation statements)

References 26 publications

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“…Nitrate content in saliva is highly regulated[85,86,193,231]. In the setting of salivary gland dysfunction, there is a decrease in salivary nitrate concentration and corollary increase in urinary excretion, thereby reducing total body nitrate content and its enterosalivary circulation[84,193,231,293]. Significantly, several diseases that share both disproportionately high rates of vascular disease and PH, including Sjögren's and systemic sclerosis[294–297], HIV[7,11], and cystic fibrosis[298] also feature dysregulated salivary flow[299–302] and altered oral microbial populations[224,303–306].…”

Section: Dysbiosis Of the Microbiome In Pulmonary Hypertension And Vascmentioning

confidence: 99%

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

Koch

Gladwin

Freeman

et al. 2017

Free Radical Biology and Medicine

145

127

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Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress. The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut. The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling, suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides. Oral supplementation with inorganic nitrate or nitrate-containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia-reperfusion injury and in pre-clinical models of PH, while traditional high-nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD. These observations highlight the potential of the microbiome in the development of novel nitrate- and nitrite-based therapeutics for PH, CVD and their risk factors.

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Section: Dysbiosis Of the Microbiome In Pulmonary Hypertension And Vascmentioning

confidence: 99%

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

Koch

Gladwin

Freeman

et al. 2017

Free Radical Biology and Medicine

145

127

View full text Add to dashboard Cite

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“…Although a large part of the anion is excreted via the kidneys, up to 25% of the circulating nitrate is actively taken up by the salivary glands and concentrated ∼10-fold in the saliva secreted from the glands (3)(4)(5). Conditions that compromise salivary gland function have been linked to decreased NO 3 − secretion from the salivary glands and increased NO 3 − levels in the serum and urine (5,6). Although nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity, most of the salivary nitrite escapes gastric conversion to NO and enters the systemic circulation, where it generates NO.…”

mentioning

confidence: 99%

Sialin ( SLC17A5 ) functions as a nitrate transporter in the plasma membrane

Qin

Liu

Sun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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177

142

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In vivo recycling of nitrate (NO 3 − ) and nitrite (NO 2 − ) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate–nitrite–NO balance. More than 25% of the circulating NO 3 − is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO 3 − to NO 2 − , which enters circulation and leads to NO generation. The transporters for NO 3 − in salivary glands have not yet been identified. Here we report that sialin ( SLC17A 5 ), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO 3 − /H + cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO 3 − or sialic acid (SA), but not by Br − , and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO 3 − -induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H + -dependent NO 3 − conductance. Importantly, adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO 3 − secretion in saliva after intake of a NO 3 − -rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO 3 − /H + transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis.

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“…The concentration of nitrate and nitrite in mixed saliva was significantly decreased, and chronic atrophic gastritis is often found in these patients [6,38]. Therefore, whether oral administration of nitrate offers guaranteed delivery of nitrite/NO into the stomach, thus providing protection against gastric injury, is worth studying.…”

Section: Discussionmentioning

confidence: 99%

“…Saliva samples were 10,000 MW filtered and diluted before assay. The concentrations of nitrate and nitrite in the saliva were detected by high-performance liquid chromatography (HPLC) as described previously [5,6]. …”

Section: Methodsmentioning

confidence: 99%

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Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats

Jin

Qin

Xia

et al. 2013

Free Radical Biology and Medicine

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Up to 25% of the circulating nitrate in blood is actively taken up, concentrated, and secreted into saliva by the salivary glands. Salivary nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity or stomach and then further converted to nitric oxide (NO) in vivo, which may play a role in gastric protection. However, whether salivary nitrate is actively secreted in human beings has not yet been determined. This study was designed to determine whether salivary nitrate is actively secreted in human beings as an acute stress response and what role salivary nitrate plays in stress-induced gastric injury. To observe salivary nitrate function under stress conditions, alteration of salivary nitrate and nitrite was analyzed among 22 healthy volunteers before and after a strong stress activity, jumping down from a platform at the height of 68m. A series of stress indexes was analyzed to monitor the stress situation. We found that both the concentration and the total amount of nitrate in mixed saliva were significantly increased in the human volunteers immediately after the jump, with an additional increase 1 h later (p < 0.01). Saliva nitrite reached a maximum immediately after the jump and was maintained 1 h later. To study the biological functions of salivary nitrate and nitrite in stress protection, we further carried out a water-immersion-restraint stress (WIRS) assay in male adult rats with bilateral parotid and submandibular duct ligature (BPSDL). Intragastric nitrate, nitrite, and NO; gastric mucosal blood flow; and gastric ulcer index (UI) were monitored and nitrate was administrated in drinking water to compensate for nitrate secretion in BPSDL animals. Significantly decreased levels of intragastric nitrate, nitrite, and NO and gastricmucosal blood flow were measured in BPSDL rats during the WIRS assay compared to sham control rats (p < 0.05). Recovery was observed in the BPSDL rats upon nitrate administration. The WIRS-induced UI was significantly higher in the BPSDL animals compared to controls, and nitrate administration rescued the WIRS-induced gastric injury in BPSDL rats. In conclusion, this study suggests that stress promotes salivary nitrate secretion and nitrite formation, which may play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway.

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Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction

Abstract: Hypofunction of the salivary glands is associated with significant changes of nitrate and nitrite levels in the saliva and urine.

Cited by 24 publications

References 26 publications

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health

Sialin ( SLC17A5 ) functions as a nitrate transporter in the plasma membrane

Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats

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