Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats
Open accessAbstract
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 68 m. 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 1h later (p<0.01). Saliva nitrite reached a maximum immediately after the jump and was maintained 1h 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 gastric mucosal 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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Approximately 25% of total circulating nitrate is actively sequestered into salivary glands and concentrated in saliva up to 20 times that in plasma, in proportion to the dietary load of nitrate.
“In proportion to the dietary load of nitrate, approximately 25% of total circulating nitrate is actively sequestered into salivary glands and concentrated in saliva up to 20 times that in plasma[73,75,82–88].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [86]
Nitrite and nitrate are important protective elements of the oral and mucosal immune response, especially in settings of stress and periodontal injury.
“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].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [86]
Nitrate content in saliva is highly regulated.
“Nitrate content in saliva is highly regulated[85,86,193,231].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [86]
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- Authors
- Jin, L., Qin, L., Xia, D., Liu, X., Fan, Z., Zhang, C., Gu, L., He, J., Ambudkar, I. S., Deng, D., & Wang, S.
- Affiliations
- Capital Medical University (CN)
- National Institutes of Health (US)
- Peking University Cancer Hospital (CN)
- Corresponding author
- Deng, Dajun
- Wang, Songlin
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 57
- Pages
- 61-67
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4059197
- OpenAlex
- W2015852791
- Cited by
- 64
- References
- 39
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 2 · 2014: 1 · 2013: 3
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (30430690, 30125042, 81170975)
- Beijing Municipal Committee for Science and Technology (Z121100005212004)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Physiology › Salivary Gland Disorders and Functions
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- salivary nitrate, salivary nitrite, nitric oxide, acute stress response, stress-induced gastric injury, gastric mucosal blood flow, gastric ulcer, water immersion stress, nitrate supplementation, gastroprotection
- MeSH terms
- Adult, Animals, Female, Gastric Juice, Gastric Mucosa, Humans, Male, Middle Aged, Nitrates, Nitrites, Parotid Gland, Regional Blood Flow, Saliva, Salivary Glands, Stomach Ulcer, Stress, Physiological, Salivary Ducts, Rats, Young Adult
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