ArticleCirculation2019
Blood Pressure-Lowering by the Antioxidant Resveratrol Is Counterintuitively Mediated by Oxidation of cGMP-Dependent Protein Kinase.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- The Effects of Resveratrol on Menopausal Cardio-metabolic Changes: A Systematic Review.Cardiovascular & hematological disorders drug targets · 2026Pooled it
- Vitamin C and Metabolic Syndrome: A Meta-Analysis of Observational Studies.Frontiers in nutrition · 2021Pooled it
- Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease.Acta physiologica (Oxford, England) · 2026Review
- Targeting PKGIα CysScience advances · 2026Article
- ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation.Redox biology · 2026Article
- Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Disulfidptosis-Related Genes as Novel Biomarkers and Therapeutic Targets in Dilated Cardiomyopathy.Journal of inflammation research · 2025Article
- Association between hypertension and oxidative balance score: data from National Health and Nutrition Examination Survey 2005-2018.Frontiers in cardiovascular medicine · 2025Article
- Therapeutic effect of targeted antioxidant natural products.Discover nano · 2024Review
- De Novo Synthesis of Resveratrol from Sucrose by Metabolically EngineeredBiomolecules · 2024Article
- Recent progress in nanotechnology-based drug carriers for resveratrol delivery.Drug delivery · 2023Review
- Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.Redox biology · 2023Review
- Resveratrol and beyond: The Effect of Natural Polyphenols on the Cardiovascular System: A Narrative Review.Biomedicines · 2023Review
- Alcohol and the vasculature: a love-hate relationship?Pflugers Archiv : European journal of physiology · 2023Review
- Intracellular Redox Behavior of Quercetin and Resveratrol Singly and in Mixtures.Molecules (Basel, Switzerland) · 2023Article
- The Role of Oxidants in Percutaneous Coronary Intervention-Induced Endothelial Dysfunction: Can We Harness Redox Signaling to Improve Clinical Outcomes?Antioxidants & redox signaling · 2023Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Oxidative Stress, Antioxidants and Hypertension.Antioxidants (Basel, Switzerland) · 2023Review
- The Effects of Antioxidant Nutraceuticals on Cellular Sulfur Metabolism and Signaling.Antioxidants & redox signaling · 2023Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe health-promoting and disease-limiting abilities of resveratrol, a natural polyphenol, has led to considerable interest in understanding the mechanisms of its therapeutic actions. The polyphenolic rings of resveratrol enable it to react with and detoxify otherwise injurious oxidants. Whilst the protective actions of resveratrol are commonly ascribed to its antioxidant activity, here we show that this is a misconception.
methodsThe ability of resveratrol to oxidize cGMP-dependent PKG1α (protein kinase 1α) was assessed in isolated rat aortic smooth muscle cells, and the mechanism of action of this polyphenol was characterized using in vitro experiments, mass spectrometry and electron paramagnetic resonance. The blood pressure of wild-type and C42S knock-in mice was assessed using implanted telemetry probes. Mice were made hypertensive by administration of angiotensin II via osmotic mini-pumps and blood pressure monitored during 15 days of feeding with chow diet containing vehicle or resveratrol.
resultsOxidation of the phenolic rings of resveratrol paradoxically leads to oxidative modification of proteins, explained by formation of a reactive quinone that oxidizes the thiolate side chain of cysteine residues; events that were enhanced in cells under oxidative stress. Consistent with these observations and its ability to induce vasodilation, resveratrol induced oxidative activation of PKG1α and lowered blood pressure in hypertensive wild-type mice, but not C42S PKG1α knock-in mice that are resistant to disulfide activation.
conclusionsResveratrol mediates lowering of blood pressure by paradoxically inducing protein oxidation, especially during times of oxidative stress, a mechanism that may be a common feature of antioxidant molecules.
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.