ReviewBritish journal of pharmacology2008
The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles.
Review in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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
45 citing papers in PubMed, 125 citations in OpenAlex.
- Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.Nitric oxide : biology and chemistry · 2023Trial
- Inorganic nitrate as a treatment for acute heart failure: a protocol for a single center, randomized, double-blind, placebo-controlled pilot and feasibility study.Journal of translational medicine · 2017Trial
- Trial
- Advances in Factors Affecting ALDH2 Activity and its Mechanisms.Cardiovascular toxicology · 2024Review
- Acetazolamide and human carbonic anhydrases: retrospect, review and discussion of an intimate relationship.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- 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
- The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design.Contemporary clinical trials communications · 2023Article
- Pharmacotherapy in patients with vasomotor disorders.International journal of cardiology. Heart & vasculature · 2023Review
- Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.Pharmacological reviews · 2022Review
- A physiologically relevant role for NO stored in vascular smooth muscle cells: A novel theory of vascular NO signaling.Redox biology · 2022Review
- Multitarget Antioxidant NO-Donor Organic Nitrates: A Novel Approach to Overcome Nitrates Tolerance, an Ex Vivo Study.Antioxidants (Basel, Switzerland) · 2022Article
- Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance.Molecules (Basel, Switzerland) · 2021Review
- Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease.Scientific reports · 2020Article
- Endothelial nitric oxide synthase-derived nitric oxide in the regulation of metabolism.F1000Research · 2020Review
- Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery.Nitric oxide : biology and chemistry · 2019Review
- Sustained Formation of Nitroglycerin-Derived Nitric Oxide by Aldehyde Dehydrogenase-2 in Vascular Smooth Muscle without Added Reductants: Implications for the Development of Nitrate Tolerance.Molecular pharmacology · 2018Article
- Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate.Molecules (Basel, Switzerland) · 2016Article
- Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.The Journal of biological chemistry · 2016Article
- Vasodilator Therapy: Nitrates and Nicorandil.Cardiovascular drugs and therapy · 2016Review
- Discovery of a series of aromatic lactones as ALDH1/2-directed inhibitors.Chemico-biological interactions · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3-electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies.
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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.