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

Jin, Luyuan; Qin, Lizheng; Xia, Dengsheng; Liu, Xibao; Fan, Zhipeng; Zhang, Chunmei; Gu, Lin; He, Junqi; Ambudkar, Indu S.; Deng, Dajun; Wang, Songlin

doi:10.1016/j.freeradbiomed.2012.12.015

Cited by 47 publications

(37 citation statements)

References 33 publications

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“…For instance, nitrite and nitrate are important protective elements of the oral and mucosal immune response, especially in settings of stress and periodontal injury[86,193,231]. Nitrite can exert pH-dependent antimicrobial effects[204,232,233] via formation of reactive secondary nitrogen oxides that can disrupt aerobic respiration[234], inhibit bacterial acid production, and disrupt biofilm formation[235–237].…”

Section: The Oral Microbiome and Bacterial Nitrate Reductionmentioning

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

133

117

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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: The Oral Microbiome and Bacterial Nitrate Reductionmentioning

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

133

117

View full text Add to dashboard Cite

show abstract

“…It was recently demonstrated that long-term supplementation of drinking water with dietary nitrate reduced stress-induced gastric damage in the bilateral parotid and submandibular gland duct ligature in rats (BPSDL) (Jin 2013). That ligature completely blocked nitrate secretion by the salivary glands, resulting in decreased gastric nitrate (60 %), nitrite (66 %), and NO (62 %) concentrations.…”

Section: Discussionmentioning

confidence: 99%

Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice

Kramkowski

Leszczyńska

Przyborowski

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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In humans, short-term supplementation with nitrate is hypotensive and inhibits platelet aggregation via an nitric oxide (NO)-dependent mechanism. In the present work, we analyzed whether short-term treatment with nitrate induces antithrombotic effects in rats and mice. Arterial thrombosis was evoked electrically in a rat model in which renovascular hypertension was induced by partial ligation of the left renal artery. In mice expressing green fluorescent protein, laser-induced thrombosis was analyzed intravitally by using confocal microscope. Sodium nitrate (NaNO3) or sodium nitrite (NaNO2) was administered orally at a dose of 0.17 mmol/kg, twice per day for 3 days. Short-term nitrate treatment did not modify thrombus formation in either rats or mice, while nitrite administration led to pronounced antithrombotic activity. In hypertensive rats, nitrite treatment resulted in a significant decrease in thrombus weight (0.50 ± 0.08 mg vs. VEH 0.96 ± 0.09 mg; p < 0.01). In addition, nitrite inhibited ex vivo platelet aggregation and thromboxane B2 (TxB2) generation and prolonged prothrombin time. These effects were accompanied by significant increases in blood NOHb concentration and plasma nitrite concentration. In contrast, nitrate did not affect ex vivo platelet aggregation or prothrombin time and led to only slightly elevated nitrite plasma concentration. In mice, nitrate was also ineffective, while nitrite led to decreased platelet accumulation in the area of laser-induced endothelial injury. In conclusion, although nitrite induced profound NO-dependent antithrombotic effects in vivo, conversion of nitrates to nitrite in rats and mice over short-term 3-day treatment was not sufficient to elicit NO-dependent antiplatelet or antithrombotic effects.

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Section: Salivamentioning

confidence: 99%

“…Blockade of salivary nitrate secretion by ligation of the sub-mandibular gland duct in rats results in decreased gastric nitrate, nitrite, and NO concentrations and exacerbates stress-induced gastric ulcers (34). The severity of gastric ulcers in these rats is reduced upon supplemental nitrate treatment (34). These gastroprotective effects appear to be mediated through the action of increased salivary nitrite, as nitrite-rich saliva results in increased gastric mucosal blood flow, a thicker mucus layer, and attenuation of the inflammatory response associated with NSAID administration in rats (23,35,36).…”

Section: Salivamentioning

confidence: 99%

Dietary intake and bio-activation of nitrite and nitrate in newborn infants

et al. 2014

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Nitrate and nitrite are commonly thought of as inert end products of nitric oxide (NO) oxidation, possibly carcinogenic food additives, or well-water contaminants. However, recent studies have shown that nitrate and nitrite play an important role in cardiovascular and gastrointestinal homeostasis through conversion back into NO via a physiological system involving enterosalivary recirculation, bacterial nitrate reductases, and enzyme-catalyzed or acidic reduction of nitrite to NO. The diet is a key source of nitrate in adults; however, infants ingest significantly less nitrate due to low concentrations in breast milk. In the mouth, bacteria convert nitrate to nitrite, which has gastro-protective effects. However, these nitrate-reducing bacteria are relatively inactive in infants. Swallowed nitrite is reduced to NO by acid in the stomach, affecting gastric blood flow, mucus production, and the gastric microbiota. These effects are likely attenuated in the less acidic neonatal stomach. Systemically, nitrite acts as a reservoir of NO bioactivity that can protect against ischemic injury, yet plasma nitrite concentrations are markedly lower in infants than in adults. The physiological importance of the diminished nitrate→nitrite→NO axis in infants and its implications in the etiology and treatment of newborn diseases such as necrotizing enterocolitis and hypoxic/ischemic injury are yet to be determined.

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

Cited by 47 publications

References 33 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

Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice

Dietary intake and bio-activation of nitrite and nitrate in newborn infants

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