Evidence map›Paper›PMID 26261901›Full record

ReviewAntioxidants & redox signaling2015

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

Andreas Daiber, Thomas Münzel

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
6.8field-weighted citation impact, top 3% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Trial
  6. The role of vascular endothelium in nitroglycerin-mediated vasodilation.British journal of clinical pharmacology · 2019
    Trial
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Andreas DaiberThe 2nd Medical Clinic, Medical Center of the Johannes Gutenberg University , Mainz, Germany .
Thomas MünzelThe 2nd Medical Clinic, Medical Center of the Johannes Gutenberg University , Mainz, Germany .
Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Indexed as

Oxidative StressAnimalsCardiovascular DiseasesEndothelium, VascularHumansNitratesOxidation-ReductionReactive Oxygen SpeciesVasodilator AgentsNitratesReactive Oxygen SpeciesVasodilator Agents

Identifiers

PMID26261901
PMCPMC4752190
OpenAlexW1786604115

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.