Nitrite in saliva increases gastric mucosal blood flow and mucus thickness
Open accessAbstract
Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to NO and related compounds, which have potential biological activity. We used an in vivo rat model as a bioassay to test effects of human saliva on gastric mucosal blood flow and mucus thickness. Gastric mucosal blood flow and mucus thickness were measured after topical administration of human saliva in HCl. The saliva was collected either after fasting (low in nitrite) or after ingestion of sodium nitrate (high in nitrite). In additional experiments, saliva was exchanged for sodium nitrite at different doses. Mucosal blood flow was increased after luminal application of nitrite-rich saliva, whereas fasting saliva had no effects. Also, mucus thickness increased in response to nitrite-rich saliva. The effects of nitrite-rich saliva were similar to those of topically applied sodium nitrite. Nitrite-mediated effects were associated with generation of NO and S-nitrosothiols. In addition, pretreatment with an inhibitor of guanylyl cyclase markedly inhibited nitrite-mediated effects on blood flow. We conclude that nitrite-containing human saliva given luminally increases gastric mucosal blood flow and mucus thickness in the rat. These effects are likely mediated through nonenzymatic generation of NO via activation of guanylyl cyclase. This supports a gastroprotective role of salivary nitrate/nitrite.
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Salivary nitrite increases gastric mucosal blood flow and mucus production, which supports gastroprotective mechanisms.
“Salivary nitrite increases gastric mucosal blood flow and mucus production, thereby supporting gastroprotective mechanisms35.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [35]
Released NO in the stomach locally contributes to increasing gastric mucosal blood flow and mucous thickness and serves as first-line host defense against swallowed pathogens.
“the released NO in the stomach is thought to locally contribute to increasing the gastric mucosal blood flow and mucous thickness to ensure the normal gastric physiology, and serves as the first-line host defense against swallowed pathogens [25,26].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [25]
Salivary nitrite increases gastric mucosal blood flow and mucous thickness.
“Salivary nitrite has been show to increase gastric mucosal blood flow and mucous thickness [7].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [7]
Dietary nitrate improves intestinal health.
“Physiological effects of increasing dietary nitrate include improving intestinal health [7]”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [7]
Oral ingestion of nitrite into the acidic environment of the stomach produces NO that augments mucus secretion, antibacterial effects of gastric fluids, and ulcer healing.
“Moreover, oral ingestion of nitrite into the acidic environment of the stomach produces NO that augments mucus secretion, antibacterial effects of gastric fluids, and ulcer healing [93–97].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [93]
Salivary nitrite increases gastric mucosal blood flow and mucus production.
“Bjorne et al demonstrated that salivary nitrite increases gastric mucosal blood flow and mucus production [93].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [93]
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“Nitrate-derived NO was shown to diffuse towards the gastric mucosa inducing local vasodilation (Björne et al., 2004; Rocha et al., 2010), the expression of genes encoding mucins, the glycoproteins that sustain the gastric mucus, and to inhibit inflammatory pathways such as those involving myeloperoxidase and the expre…”
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- Authors
- Björne, H., Petersson, J., Phillipson, M., Weitzberg, E., Holm, L., & Lundberg, J. O.
- Affiliations
- Karolinska University Hospital (SE)
- Uppsala University (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Lundberg, Jon O.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-01-01
- Volume
- 113
- Issue
- 1
- Pages
- 106-114
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2112012050
- Cited by
- 246
- References
- 62
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 15 · 2016: 10 · 2015: 17 · 2014: 11 · 2013: 16 · 2012: 14
- FWCI
- 10.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Hjärt-Lungfonden
- Karolinska Institutet
- Vetenskapsrådet
- Ekhagastiftelsen
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- salivary nitrite, salivary nitrate, gastric mucosal blood flow, nitric oxide, S-nitrosothiols, guanylate cyclase, gastroprotection, oral bacteria, sodium nitrite, gastric acid
- MeSH terms
- Animals, Blood Flow Velocity, Gastric Mucosa, Humans, Kinetics, Male, Nitrates, Nitrites, Oxidation-Reduction, Regional Blood Flow, Saliva, Sodium Nitrite, Rats, Sprague-Dawley, Rats
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