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 48 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

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: 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

145

127

View full text Add to dashboard Cite

show abstract

“…Oxidative stress is defined as the overproduction of free radicals, such as reactive oxygen species and reactive nitrogen species accompanied by the inability of endogenous defensive antioxidant enzymes to detoxify these free radicals (11). Nitrates, a nitric oxide (NO) metabolite present in different tissues and the chief reactive nitrogen species constituent, is a marker of oxidative stress and is implicated in associated disorders (13); NO increases in acute anxiety (14,15). Furthermore, various animal studies have reported higher NOx in the hippocampus and brain cortex of a stressed animal (16).…”

Section: Introductionmentioning

confidence: 99%

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety

2017

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Abstract. There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA-(0.5 mg/kg) and escitalopram-(ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.

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

Cited by 48 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

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety

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

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