Cited by 4Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionPhytochemicals and Antioxidant Activities

Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases

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Pang, Baoxing, Qi, Xingyun, Zhang, Huiliang·2025·Biomolecules

Abstract

Cardiovascular diseases (CVDs), which include multiple disorders of the heart and blood vessels, are the leading causes of death. Nitric oxide (NO) is a vasodilator that regulates vascular tension. Endogenous NO is produced via the L-arginine–nitric oxide synthase (NOS) pathway. In conditions of cardiovascular dysfunction, NOS activity is impaired, leading to NO deficiency. In turn, the reduction in NO bioactivity exacerbates the pathogenesis of CVDs. Exogenous intake of inorganic nitrate supplements endogenous production via the nitrate–nitrite–NO pathway to maintain the NO supply. Salivary glands play an essential role in the conversion of nitrate to NO, with approximately 25% of circulating nitrate being absorbed and secreted into saliva. As a result, salivary nitrate concentrations can exceed that in the blood by more than tenfold. This recycled nitrate in saliva serves as a reservoir for NO and performs NO-like functions when endogenous NO production is insufficient. In this review, we summarize the emerging benefits of dietary nitrate in CVDs, with a particular focus on salivary-gland-mediated nitrate recirculation in maintaining NO bioavailability and cardiovascular homeostasis. Salivary-gland-mediated nitrate recirculation provides a novel perspective for potential intervention of CVDs.

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Crossref · 10.3390/biom15030439

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  • The enterosalivary circulation maintains a circulating nitrate reservoir that supports NO production, particularly under hypoxic conditions where endogenous NOS activity is limited.

    “This enterosalivary circulation, comprising intestinal absorption, systemic distribution, salivary concentration, and re-swallowing, maintains a circulating nitrate reservoir that supports NO production, particularly under hypoxic conditions where endogenous NO synthase (NOS) activity is limited [27,28].”

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Authors
Pang, B., Qi, X., & Zhang, H.
Affiliations
  • Temple University (US)
  • Rutgers, The State University of New Jersey (US)
Corresponding author
Zhang, Huiliang
Venue
Biomolecules
Publisher
MDPI AG
Published
2025-03-19
Volume
15
Issue
3
Pages
439
ISSN
2218-273X (ISSN-L)
OpenAlex
W4408618319
Cited by
3
References
113
Citations by year
2026: 3
FWCI
0.39
Type
journal article
Language
en
Open access
Locations
  • Biomolecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (R35GM151226, R35GM151096, 2217757)
  • National Science Foundation (R35GM151226, R35GM151096, 2217757)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Keywords
salivary glands, nitric oxide bioavailability, cardiovascular disease, dietary nitrate, nitrate-nitrite-NO pathway, nitric oxide synthase, salivary nitrate, cardiovascular homeostasis, vasodilation
MeSH terms
Animals, Cardiovascular Diseases, Humans, Nitrates, Nitric Oxide, Saliva, Salivary Glands, Nitric Oxide Synthase

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