ArticleThe Journal of clinical investigation2003
Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 146 citations in OpenAlex.
- 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
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- Article
- Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion.Antioxidants (Basel, Switzerland) · 2021Article
- Uremic Toxins and Vascular Dysfunction.Toxins · 2020Review
- Reactive oxygen species in cardiovascular health and disease: special references to nitric oxide, hydrogen peroxide, and Rho-kinase.Journal of clinical biochemistry and nutrition · 2020Review
- Curcumin supplementation attenuates the decrease in endothelial function following eccentric exercise.Journal of exercise nutrition & biochemistry · 2019Article
- Deletion of endothelial arginase 1 does not improve vasomotor function in diabetic mice.Physiological reports · 2018Article
- Diverse Functions of Endothelial NO Synthases System: NO and EDH.Journal of cardiovascular pharmacology · 2016Review
- The Human Microcirculation: Regulation of Flow and Beyond.Circulation research · 2016Review
- Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.Pharmacology research & perspectives · 2015Article
- Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction--a novel mechanism for maintaining vascular function.Journal of hematology & oncology · 2014Review
- Amelioration of salt-induced vascular dysfunction in mesenteric arteries of Dahl salt-sensitive rats by missense mutation of extracellular superoxide dismutase.American journal of physiology. Heart and circulatory physiology · 2014Article
- Regulation of cellular communication by signaling microdomains in the blood vessel wall.Pharmacological reviews · 2014Review
- Redox signaling in cardiovascular health and disease.Free radical biology & medicine · 2013Review
- Nitric oxide synthases in heart failure.Antioxidants & redox signaling · 2013Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 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 vasodilating factors, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived H2O2 is an EDHF in mesenteric arteries of mice and humans and in porcine coronary microvessels. However, the mechanism for the endothelial production of H2O2 as an EDHF remains to be elucidated. In this study, we tested our hypothesis that Cu,Zn-superoxide dismutase (Cu,Zn-SOD) plays a pivotal role in endothelium-dependent hyperpolarization, using control and Cu,Zn-SOD-/- mice. In mesenteric arteries, EDHF-mediated relaxations and hyperpolarizations were significantly reduced in Cu,Zn-SOD-/- mice with no inhibitory effect of catalase, while endothelium-independent relaxations and hyperpolarizations were preserved. Endothelial H2O2 production also was significantly reduced in Cu,Zn-SOD-/- mice. In Langendorff isolated heart, bradykinin-induced increase in coronary flow was significantly reduced in Cu,Zn-SOD-/- mice, again with no inhibitory effect of catalase. The exogenous SOD mimetic tempol significantly improved EDHF-mediated relaxations and hyperpolarizations and coronary flow response in Cu,Zn-SOD-/- mice. These results prove the novel concept that endothelial Cu,Zn-SOD plays an important role as an "EDHF synthase" in mice, in addition to its classical role to scavenge superoxide anions.
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.