ArticleThe Journal of physiology2014
Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Comparative Efficacy of Nutritional Supplements in Modulating Lung Function and Exercise Capacity in COPD Patients: A Network Meta-Analysis.International journal of chronic obstructive pulmonary disease · 2025Pooled it
- Trial
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases.Biomolecules · 2025Review
- Effects of a Three-Day vs. Six-Day Exposure to Normobaric Hypoxia on the Cardiopulmonary Function of Rats.Current issues in molecular biology · 2025Article
- Dietary nitrate supplementation very slightly mitigates the oxidative stress induced by high-intensity training performed in normobaric hypoxia.Biology of sport · 2025Article
- Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025Article
- The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy.Nutrients · 2024Review
- Effects of Normobaric Hypoxia and Adrenergic Blockade over 72 h on Cardiac Function in Rats.International journal of molecular sciences · 2023Article
- Plasma Metabolite Profiles Associated with the Amount and Source of Meat and Fish Consumption and the Risk of Type 2 Diabetes.Molecular nutrition & food research · 2022Article
- Relaxin does not prevent development of hypoxia-induced pulmonary edema in rats.Pflugers Archiv : European journal of physiology · 2022Article
- Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.Life (Basel, Switzerland) · 2022Review
- Nitrate exposure reprograms hepatic amino acid and nutrient sensing pathways prior to exercise: A metabolomic and transcriptomic investigation in zebrafishFrontiers in molecular biosciences · 2022Article
- Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load.Pflugers Archiv : European journal of physiology · 2021Article
- Nitric oxide signalling in kidney regulation and cardiometabolic health.Nature reviews. Nephrology · 2021Review
- Enhanced Placental Mitochondrial Respiration in Tibetan Women at High Altitude.Frontiers in physiology · 2021Article
- Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish.The Journal of nutrition · 2019Article
- Influence of dietary inorganic nitrate on blood pressure and vascular function in hypertension: prospective implications for adjunctive treatment.Journal of applied physiology (Bethesda, Md. : 1985) · 2019Article
- Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Dietary nitrate's effects on exercise performance in heart failure with reduced ejection fraction (HFrEF).Biochimica et biophysica acta. Molecular basis of disease · 2019Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l(-1) NaCl (as control) or 0.7 mmol l(-1) NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics.
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Registered trials
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