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Cited by 13Neurological Disease Mechanisms and TreatmentsNitric Oxide and Endothelin EffectsDementia and Cognitive Impairment Research

Multifaceted role of nitric oxide in vascular dementia

Open access
Yang, Yi, Ma, Kangrong, Li, Shun, Xiong, Tianqing·2025·Medical Gas Research
DOI 10.4103/mgr.medgasres-d-24-00158PMC PMC12124705
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Abstract

Vascular dementia is a highly heterogeneous neurodegenerative disorder induced by a variety of factors. Currently, there are no definitive treatments for the cognitive dysfunction associated with vascular dementia. However, early detection and preventive measures have proven effective in reducing the risk of onset and improving patient prognosis. Nitric oxide plays an integral role in various physiological and pathological processes within the central nervous system. In recent years, nitric oxide has been implicated in the regulation of synaptic plasticity and has emerged as a crucial factor in the pathophysiology of vascular dementia. At different stages of vascular dementia, nitric oxide levels and bioavailability undergo dynamic alterations, with a marked reduction in the later stages, which significantly contributes to the cognitive deficits associated with the disease. This review provides a comprehensive review of the emerging role of nitric oxide in the physiological and pathological processes underlying vascular dementia, focusing on its effects on synaptic dysfunction, neuroinflammation, oxidative stress, and blood‒brain barrier integrity. Furthermore, we suggest that targeting the nitric oxide soluble guanylate cyclase-cyclic guanosine monophosphate pathway through specific therapeutic strategies may offer a novel approach for treating vascular dementia, potentially improving both cognitive function and patient prognosis. The review contributes to a better understanding of the multifaceted role of nitric oxide in vascular dementia and to offering insights into future therapeutic interventions.

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Registry

Crossref · 10.4103/mgr.medgasres-d-24-00158

Cites

137 of 137 references verified0 citation errors · 0 not checkable

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Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • NO is a multifunctional signalling molecule involved in vascular regulation, neurotransmission, inflammation, and neuroprotection-processes that decline with ageing.

    “Interest in dietary nitrate has increased with the recognition of NO as a multifunctional signalling molecule involved in vascular regulation, neurotransmission, inflammation, and neuroprotection—processes that decline with ageing [17].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [17]

    The Physiological Role of Nitric Oxide section describes NO’s roles in vascular regulation, neurotransmission, and inflammatory responses; the Source of Nitric Oxide section also describes a neuroprotective effect. The cited passages do not establish that these processes decline with ageing. Their references to aged mitochondria are not evidence for that broader ageing claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Approximately 25% of circulating nitrate is concentrated in saliva and converted to nitrite.

    “approximately 25% of circulating nitrate is concentrated in saliva and converted to nitrite”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [17]

    The Source of Nitric Oxide section (page not available) says that nitrates are converted into nitrites and then nitric oxide. It does not state that approximately 25% of circulating nitrate is concentrated in saliva or that the conversion occurs there. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The enterosalivary cycle represents a critical regulatory step that may become less efficient with age.

    “The enterosalivary cycle, in which approximately 25% of circulating nitrate is concentrated in saliva and converted to nitrite, represents a critical regulatory step that may become less efficient with age [17,231].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [17]

    The Source of Nitric Oxide section says dietary nitrates are converted to nitrites and then nitric oxide, but it does not discuss the enterosalivary cycle as a critical regulatory step or say that the cycle becomes less efficient with age. Searches for the cycle, saliva, and the claimed 25% figure found no passage addressing those points; the paper's pages are not specified in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • Other medications, including XOR inhibitors (e.g., allopurinol) and drugs that affect salivary flow or gastrointestinal motility, may further modify nitrate bioactivation.

    “Other medications, including xanthine oxidase (XOR) inhibitors (e.g., allopurinol) and drugs that affect salivary flow or gastrointestinal motility, may further modify nitrate bioactivation [17,272].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [17]

    The Source of Nitric Oxide section says dietary nitrates are converted to nitrites and then nitric oxide, but does not address whether medications modify that conversion. Searches for allopurinol or XOR inhibitors, salivary flow, and gastrointestinal motility found no relevant passage in our copy; the paper is not truncated. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Cites

1 retracted

Flagged first, then by citations

2 of the 139 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. [18]Ignarro LJ Nitric oxide: a unique endogenous signaling molecule in vascular biology (Nobel lecture) Angew Chem Int Ed Engl 1999 38 1882 1892 34182699
  2. [20]Furchgott RF Endothelium-derived relaxing factor: discovery, early studies, and identifcation as nitric oxide (Nobel lecture) Angew Chem Int Ed Engl 1999 38 1870 1880 34182659
  3. [81]Chen XY Wan SF Yao NN Inhibition of the immunoproteasome LMP2 ameliorates ischemia/hypoxia-induced blood-brain barrier injury through the Wnt/β-catenin signalling pathway Mil Med Res 2021 8 62 34857032 PMC8641178
  4. [84]Zhu HY Hong FF Yang SL The roles of nitric oxide synthase/nitric oxide pathway in the pathology of vascular dementia and related therapeutic approaches Int J Mol Sci 2021 22 33926146 PMC8123648

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Authors
Yang, Y., Ma, K., Li, S., & Xiong, T.
Affiliations
  • Yangzhou University (CN)
  • University of Pittsburgh (US)
Corresponding author
  • Li, Shun
  • Xiong, Tianqing
ORCID
Venue
Medical Gas Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2025-04-29
Volume
15
Issue
4
Pages
496-506
ISSN
2045-9912 (ISSN-L)
DOI
10.4103/mgr.medgasres-d-24-00158
PMC
PMC12124705
OpenAlex
W4409910638
Cited by
13
References
139
Citations by year
2026: 12 · 2025: 1
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Medical Gas Research (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
nitric oxide, vascular dementia, synaptic plasticity, synaptic dysfunction, neuroinflammation, oxidative stress, blood-brain barrier integrity, soluble guanylate cyclase, cyclic GMP, cognitive impairment, neurodegeneration, therapeutic target
MeSH terms
Animals, Humans, Nitric Oxide, Dementia, Vascular, Oxidative Stress

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