ArticleProceedings of the National Academy of Sciences of the United States of America2005
An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- Vasodilators for women undergoing fertility treatment.The Cochrane database of systematic reviews · 2018Pooled it
- ALDH2 gene G487A polymorphism and coronary artery disease: a meta-analysis including 5644 participants.Journal of cellular and molecular medicine · 2018Pooled it
- Influence of the aldehyde dehydrogenase 2 polymorphism on the vasodilatory effect of nitroglycerin in infants with congenital heart disease and pulmonary arterial hypertension.European journal of clinical pharmacology · 2019Trial
- Continuous transdermal nitroglycerin therapy for menopausal hot flashes: a single-arm, dose-escalation trial.Menopause (New York, N.Y.) · 2016Trial
- Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates.Clinical research in cardiology : official journal of the German Cardiac Society · 2012Trial
- Neuroinflammatory and Redox Responses in a Rat Model of NTG-Induced Migraine.International journal of molecular sciences · 2025Article
- Nitric Oxide in Biomaterial-Based Therapies for Coronary Heart Disease: Mechanistic Insights, Current Advances, and Translational Prospects.Biomaterials research · 2025Review
- Nitric Oxide Releasing Nanomaterials for Cardiovascular Applications.JACC. Basic to translational science · 2024Review
- HCN2 Ion Channels Drive Pain in Rodent Models of Migraine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Autonomic Dysreflexia following Spinal Cord Injury.Asian journal of neurosurgery · 2022Review
- Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance.Molecules (Basel, Switzerland) · 2021Review
- The Effect of Increasing Donor Age on Myocardial Ischemic Tolerance in a Rodent Model of Donation After Circulatory Death.Transplantation direct · 2021Article
- Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms.Applied materials today · 2021Review
- The clinical effects of l-arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon.Journal of the European Academy of Dermatology and Venereology : JEADV · 2019Review
- A comparison of CRISPR/Cas9 and siRNA-mediated ALDH2 gene silencing in human cell lines.Molecular genetics and genomics : MGG · 2018Article
- Vascular Contributions to Migraine: Time to Revisit?Frontiers in cellular neuroscience · 2018Article
- Organic mononitrites of 1,2-propanediol act as an effective NO-releasing vasodilator in pulmonary hypertension and exhibit no cross-tolerance with nitroglycerin in anesthetized pigs.Drug design, development and therapy · 2018Article
- Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia.Redox biology · 2017Article
- The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat.Frontiers in neurology · 2017Article
- Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.The Journal of biological chemistry · 2016Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiovascular biology. Recent evidence suggests an unexpected role for mitochondria. We show here that bioconversion by mitochondria of clinically relevant concentrations of GTN results in activation of guanylate cyclase, production of cGMP, vasodilation in vitro, and lowered blood pressure in vivo, which are eliminated by genetic deletion of the mitochondrial aldehyde dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative nitro(so)-vasodilators is unaffected. In mtALDH(-/-) mice and their isolated vascular tissue, GTN bioactivity can still be generated, but only at substantially higher concentrations of GTN and by a mechanism that does not exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity derived from therapeutic levels of GTN, and, more generally, mitochondria can serve as a source of NO-based cellular signals that may originate independently of NO synthase activity.
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.