ArticleNitric oxide : biology and chemistry2020
Nitrate uptake and metabolism in human skeletal muscle cell cultures.
Article in Nitric oxide : biology and chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Effects of Dietary Nitrates on Time Trial Performance in Athletes with Different Training Status: Systematic Review.Nutrients · 2020Pooled it
- Beetroot juice supplementation enhances the effects of blood flow restriction training on lower limb strength and vertical jump performance under fatigue in male university students: a randomized, double-blind, placebo-controlled study.Journal of the International Society of Sports Nutrition · 2026Trial
- Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population.Pharmaceutical research · 2020Trial
- Influence of exercise training on nitric oxide pathways and their physiological effects.Redox biology · 2026Review
- The compartmentalization model of nitrate homeostasis: Role of the salivary glands, skeletal muscle, and liver.EXCLI journal · 2026Review
- Effect of Oral Versus Nasal Breathing on Muscular Performance, Muscle Oxygenation, and Post-Exercise Recovery.Sports (Basel, Switzerland) · 2025Article
- NitrOFF: An Engineered Fluorescent Biosensor to Illuminate Nitrate Transport in Living Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Nitrate as Warden of Nitric Oxide Homeostasis in Mammals.Nutrients · 2025Review
- NitrOFF: An engineered fluorescent biosensor to illuminate nitrate transport in living cells.bioRxiv : the preprint server for biology · 2025Article
- Role of oral and gut microbiomes in enterosalivary nitrate metabolism and their effects on systemic disease.Frontiers in cellular and infection microbiology · 2025Review
- Long-term nitrate administration modulates sialin gene expression in the main tissues of male Wistar rats with type 2 diabetes.EXCLI journal · 2025Article
- Type 2 diabetes-related sarcopenia: role of nitric oxide.Nutrition & metabolism · 2024Review
- Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence andNutrients · 2024Article
- Article
- High nitrate levels in skeletal muscle contribute to nitric oxide generation via a nitrate/nitrite reductive pathway in mice that lack the nNOS enzyme.Frontiers in physiology · 2024Article
- Individualised Exercise Training Enhances Antioxidant Buffering Capacity in Idiopathic Pulmonary Fibrosis.Antioxidants (Basel, Switzerland) · 2023Article
- Effects of Dietary Nitrate Supplementation on Performance during Single and Repeated Bouts of Short-Duration High-Intensity Exercise: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Altered sialin mRNA gene expression in type 2 diabetic male Wistar rats: implications for nitric oxide deficiency.Scientific reports · 2023Article
- Distribution of dietary nitrate and its metabolites in rat tissues afterScientific reports · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Several studies show that dietary nitrate enhances exercise performance, presumably by increasing muscle blood flow and improving oxygen utilization. These effects are likely mediated by nitrate metabolites, including nitrite and nitric oxide (NO). However, the mechanisms of nitrate production, storage, and metabolism to nitrite and NO in skeletal muscle cells are still unclear. We hypothesized that exogenous nitrate can be taken up and metabolized to nitrite/NO inside the skeletal muscle. We found rapid uptake of exogeneous nitrate in both myoblasts and myotubes, increasing nitrite levels in myotubes, but not myoblasts. During differentiation we found increased expression of molybdenum containing proteins, such as xanthine oxidoreductase (XOR) and the mitochondrial amidoxime-reducing component (MARC); nitrate and nitrite reductases. Sialin, a known nitrate transporter, was detected in myoblasts; nitrate uptake decreased after sialin knockdown. Inhibition of chloride channel 1 (CLC1) also led to significantly decreased uptake of nitrate. Addition of exogenous nitrite, which resulted in higher intracellular nitrite levels, increased intracellular cGMP levels in myotubes. In summary, our results demonstrate for the first time the presence of the nitrate/nitrite/NO pathway in skeletal muscle cells, namely the existence of strong uptake of exogenous nitrate into cells and conversion of intracellular nitrate to nitrite and NO. Our results further support our previously formulated hypothesis about the importance of the nitrate to nitrite to NO intrinsic reduction pathways in skeletal muscles, which likely contributes to improved exercise tolerance after nitrate ingestion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.