ArticleThe Journal of clinical investigation2011
Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 2, Multi-Center, Open-label, Randomized, Parallel-Dose Study to Determine the Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)
A Phase 2, Multicenter, Open-Label Study to Evaluate the Intermediate/Long Term Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Pooled it
- Trial
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- 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
- Inorganic nitrates to prevent in-stent restenosis. Is nitric oxide the Philosopher's stone?EClinicalMedicine · 2025Article
- The NITRATE-OCT study-inorganic nitrate reduces in-stent restenosis in patients with stable coronary artery disease: a double-blind, randomised controlled trial.EClinicalMedicine · 2024Article
- NaHS protects brain, heart, and lungs as remote organs from renal ischemia/reperfusion-induced oxidative stress in male and female rats.BMC nephrology · 2024Article
- Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases.Current atherosclerosis reports · 2024Review
- Bringing Nitric Oxide to the Molybdenum World-A Personal Perspective.Molecules (Basel, Switzerland) · 2023Review
- Human and rodent red blood cells do not demonstrate xanthine oxidase activity or XO-catalyzed nitrite reduction to NO.Free radical biology & medicine · 2021Article
- Pro-Aging Effects of Xanthine Oxidoreductase Products.Antioxidants (Basel, Switzerland) · 2020Review
- Arginine affects growth and integrity of grass carp enterocytes by regulating TOR signaling pathway and tight junction proteins.Fish physiology and biochemistry · 2019Article
- Putting xanthine oxidoreductase and aldehyde oxidase on the NO metabolism map: Nitrite reduction by molybdoenzymes.Redox biology · 2018Review
- The Hemoglobin Homolog Cytoglobin in Smooth Muscle Inhibits Apoptosis and Regulates Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- 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
- Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase.Journal of neurotrauma · 2017Article
- My Continuing Evolution as a Surgeon-Scientist: A Decade after the Jacobson Promising Investigator Award.Journal of the American College of Surgeons · 2017Article
- Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop.Journal of the American Heart Association · 2016Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Vascular disease, a significant cause of morbidity and mortality in the developed world, results from vascular injury. Following vascular injury, damaged or dysfunctional endothelial cells and activated SMCs engage in vasoproliferative remodeling and the formation of flow-limiting intimal hyperplasia (IH). We hypothesized that vascular injury results in decreased bioavailability of NO secondary to dysregulated arginine-dependent NO generation. Furthermore, we postulated that nitrite-dependent NO generation is augmented as an adaptive response to limit vascular injury/proliferation and can be harnessed for its protective effects. Here we report that sodium nitrite (intraperitoneal, inhaled, or oral) limited the development of IH in a rat model of vascular injury. Additionally, nitrite led to the generation of NO in vessels and SMCs, as well as limited SMC proliferation via p21Waf1/Cip1 signaling. These data demonstrate that IH is associated with increased arginase-1 levels, which leads to decreased NO production and bioavailability. Vascular injury also was associated with increased levels of xanthine oxidoreductase (XOR), a known nitrite reductase. Chronic inhibition of XOR and a diet deficient in nitrate/nitrite each exacerbated vascular injury. Moreover, established IH was reversed by dietary supplementation of nitrite. The vasoprotective effects of nitrite were counteracted by inhibition of XOR. These data illustrate the importance of nitrite-generated NO as an endogenous adaptive response and as a pathway that can be harnessed for therapeutic benefit.
Indexed as
Identifiers
What OpenQuestion holds
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.