ArticleCirculation2012
Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 109 citations in OpenAlex.
- Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.Journal of the American Heart Association · 2017Trial
- Effect of pre-exercise dietary nitrate on skeletal muscle blood flow in a rat model of pulmonary hypertension.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Beneficial effects of magnesium nitrate on disease severity in male rats with monocrotaline-induced pulmonary hypertension.Physiological reports · 2025Article
- Bringing Nitric Oxide to the Molybdenum World-A Personal Perspective.Molecules (Basel, Switzerland) · 2023Review
- Combination Therapy in Pulmonary Arterial Hypertension-Targeting the Nitric Oxide and Prostacyclin Pathways.Journal of cardiovascular pharmacology and therapeutics · 2021Review
- Bronchopulmonary dysplasia is associated with reduced oral nitrate reductase activity in extremely preterm infants.Redox biology · 2021Article
- Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway.Frontiers in pharmacology · 2021Review
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Preventive effects of nitrate-rich beetroot juice supplementation on monocrotaline-induced pulmonary hypertension in rats.PloS one · 2021Article
- Airway nitrite is increased in extremely preterm infants with bronchopulmonary dysplasia.Respiratory research · 2020Article
- Nutraceuticals in the Treatment of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2020Review
- Common Vascular Toxicities of Cancer Therapies.Cardiology clinics · 2019Review
- Nutraceuticals as a potential adjunct therapy toward improving vascular health in CKD.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Review
- Thiol-Redox Regulation in Lung Development and Vascular Remodeling.Antioxidants & redox signaling · 2019Review
- Inhaled nebulized nitrite and nitrate therapy in a canine model of hypoxia-induced pulmonary hypertension.Nitric oxide : biology and chemistry · 2019Article
- Putting xanthine oxidoreductase and aldehyde oxidase on the NO metabolism map: Nitrite reduction by molybdoenzymes.Redox biology · 2018Review
- Things We "kNOw" and Do Not "kNOw" about Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2018Article
- Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health.Free radical biology & medicine · 2017Review
- Nitrite Prevents Right Ventricular Failure and Remodeling Induced by Pulmonary Artery Banding.Journal of cardiovascular pharmacology · 2017Article
- Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways.BioMed research international · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPulmonary hypertension (PH) is a multifactorial disease characterized by increased pulmonary vascular resistance and right ventricular failure; morbidity and mortality remain unacceptably high. Loss of nitric oxide (NO) bioactivity is thought to contribute to the pathogenesis of PH, and agents that augment pulmonary NO signaling are clinically effective in the disease. Inorganic nitrate (NO(3)(-)) and nitrite (NO(2)(-)) elicit a reduction in systemic blood pressure in healthy individuals; this effect is underpinned by endogenous and sequential reduction to NO. Herein, we determined whether dietary nitrate and nitrite might be preferentially reduced to NO by the hypoxia associated with PH, and thereby offer a convenient, inexpensive method of supplementing NO functionality to reduce disease severity. METHODS AND
resultsDietary nitrate reduced the right ventricular pressure and hypertrophy, and pulmonary vascular remodeling in wild-type mice exposed to 3 weeks of hypoxia; this beneficial activity was mirrored largely by dietary nitrite. The cytoprotective effects of dietary nitrate were associated with increased plasma and lung concentrations of nitrite and cGMP. The beneficial effects of dietary nitrate and nitrite were reduced in mice lacking endothelial NO synthase or treated with the xanthine oxidoreductase inhibitor allopurinol.
conclusionsThese data demonstrate that dietary nitrate, and to a lesser extent dietary nitrite, elicit pulmonary dilatation, prevent pulmonary vascular remodeling, and reduce the right ventricular hypertrophy characteristic of PH. This favorable pharmacodynamic profile depends on endothelial NO synthase and xanthine oxidoreductase -catalyzed reduction of nitrite to NO. Exploitation of this mechanism (ie, dietary nitrate/nitrite supplementation) represents a viable, orally active therapy for PH.
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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.