ArticleThe Journal of clinical investigation2000
Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
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Who cites it
203 citing papers in PubMed, 716 citations in OpenAlex.
- Reduced flow-and acetylcholine-induced dilations in visceral compared to subcutaneous adipose arterioles in human morbid obesity.Microcirculation (New York, N.Y. : 1994) · 2015Trial
- FTO/m6A Regulate Prenatal Nicotine-Induced eNOS Uncoupling and BP Susceptibility.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Glutathione/Selenite Interaction Products as Potent Vascular Smooth Muscle Tone Modulators with Antihypertensive Effects in Spontaneously Hypertensive Rats.Biological trace element research · 2026Article
- Endothelial Mitochondrial Dysfunction in INOCA and Coronary Microvascular Dysfunction: Mechanisms, Sex Differences, and Therapeutic Implications.Journal of cardiovascular development and disease · 2026Review
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Association of reduced Cu,Zn-superoxide dismutase with coronary microvascular dysfunction-An observational study of oxidative stress markers.International journal of cardiology. Heart & vasculature · 2026Article
- NO- and S-nitrosothiols-dependent relaxation in large and small resistance blood vessels.Frontiers in physiology · 2026Review
- The Endothelium as a Central Mediator of Exercise-Induced Metabolism and Communication.Exercise and sport sciences reviews · 2026Review
- The role of NO, HBasic research in cardiology · 2025Article
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Coronary Microvascular Dysfunction is Associated with Augmented Lysosomal Signaling in Hypercholesterolemic Mice.bioRxiv : the preprint server for biology · 2024Article
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System.Physiology (Bethesda, Md.) · 2024Review
- GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens.Frontiers in pharmacology · 2024Article
- The Role of Oxidants in Percutaneous Coronary Intervention-Induced Endothelial Dysfunction: Can We Harness Redox Signaling to Improve Clinical Outcomes?Antioxidants & redox signaling · 2023Review
- Coronary Microvascular Spasm: Clinical Presentation and Diagnosis.European cardiology · 2023Review
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study.Biomedicines · 2022Review
143 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several endothelium-derived relaxing factors, such as prostacyclin, nitric oxide (NO), and the previously unidentified endothelium-derived hyperpolarizing factor (EDHF). In this study, we examined our hypothesis that hydrogen peroxide (H(2)O(2)) derived from endothelial NO synthase (eNOS) is an EDHF. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine (ACh) were markedly attenuated in small mesenteric arteries from eNOS knockout (eNOS-KO) mice. In the eNOS-KO mice, vasodilating and hyperpolarizing responses of vascular smooth muscle per se were fairly well preserved, as was the increase in intracellular calcium in endothelial cells in response to ACh. Antihypertensive treatment with hydralazine failed to improve the EDHF-mediated relaxation. Catalase, which dismutates H(2)O(2) to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K(+) channel opener levcromakalim. Exogenous H(2)O(2) elicited similar relaxation and hyperpolarization in endothelium-stripped arteries. Finally, laser confocal microscopic examination with peroxide-sensitive fluorescence dye demonstrated that the endothelium produced H(2)O(2) upon stimulation by ACh and that the H(2)O(2) production was markedly reduced in eNOS-KO mice. These results indicate that H(2)O(2) is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.
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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.