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

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 car...

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Main Authors: Baoxing Pang, Xingyun Qi, Huiliang Zhang
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/3/439
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author Baoxing Pang
Xingyun Qi
Huiliang Zhang
author_facet Baoxing Pang
Xingyun Qi
Huiliang Zhang
author_sort Baoxing Pang
collection DOAJ
description 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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spelling doaj-art-03bca56554ab405fa5b051f750ac4dbf2025-08-20T03:43:02ZengMDPI AGBiomolecules2218-273X2025-03-0115343910.3390/biom15030439Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular DiseasesBaoxing Pang0Xingyun Qi1Huiliang Zhang2Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USADepartment of Biology, Rutgers University, Camden, NJ 08103, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USACardiovascular 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.https://www.mdpi.com/2218-273X/15/3/439cardiovascular diseasenitratenitritenitric oxide (NO)nitrate–nitrite–NO pathwaysalivary gland
spellingShingle Baoxing Pang
Xingyun Qi
Huiliang Zhang
Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
Biomolecules
cardiovascular disease
nitrate
nitrite
nitric oxide (NO)
nitrate–nitrite–NO pathway
salivary gland
title Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
title_full Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
title_fullStr Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
title_full_unstemmed Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
title_short Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
title_sort salivary gland mediated nitrate recirculation as a modulator for cardiovascular diseases
topic cardiovascular disease
nitrate
nitrite
nitric oxide (NO)
nitrate–nitrite–NO pathway
salivary gland
url https://www.mdpi.com/2218-273X/15/3/439
work_keys_str_mv AT baoxingpang salivaryglandmediatednitraterecirculationasamodulatorforcardiovasculardiseases
AT xingyunqi salivaryglandmediatednitraterecirculationasamodulatorforcardiovasculardiseases
AT huiliangzhang salivaryglandmediatednitraterecirculationasamodulatorforcardiovasculardiseases