ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2013
Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via α-adrenergic receptors.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Device-guided slow breathing alters postprandial oxidative stress in young adult males: A randomized sham-controlled crossover trial.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2023Trial
- Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021Trial
- Nicotine-containing products and the cardiovascular system: mechanisms and global health implications.Nature reviews. Cardiology · 2026Review
- Article
- Reactive oxygen species elevations in human immune cell subsets during sepsis are mitigated by norepinephrine and N-acetylcysteine.World journal of critical care medicine · 2025Article
- TBrain, behavior, and immunity · 2025Article
- Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?Physiology (Bethesda, Md.) · 2024Review
- Aging and "Age-Related" Diseases - What Is the Relation?Aging and disease · 2024Review
- Renal denervation ameliorated salt-induced hypertension by improving cardiac work, cardiac enzyme and oxidative balance in Sprague-Dawley rats.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
- Impact of norepinephrine on immunity and oxidative metabolism in sepsis.Frontiers in immunology · 2023Review
- Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects.International journal of molecular sciences · 2022Article
- Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Pathogenesis of (smoking-related) non-communicable diseases-Evidence for a common underlying pathophysiological pattern.Frontiers in physiology · 2022Review
- Impact of acute antioxidant supplementation on vascular function and autonomic nervous system modulation in young adults with PTSD.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase.International journal of molecular medicine · 2021Article
- The role of oxidative stress in cardiovascular disease caused by social isolation and loneliness.Redox biology · 2020Review
- Norepinephrine Induces Lung Microvascular Endothelial Cell Death by NADPH Oxidase-Dependent Activation of Caspase-3.Oxidative medicine and cellular longevity · 2020Article
- Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells.Scientific reports · 2019Article
- Autonomic regulation of T-lymphocytes: Implications in cardiovascular disease.Pharmacological research · 2019Review
- Loneliness, Social Isolation, and Cardiovascular Health.Antioxidants & redox signaling · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter norepinephrine (NE) increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. After NE (50 pg/ml, 50 ng/ml, and 50 μg/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91(phox), p22(phox), and p67(phox)) was assessed using real-time RT-PCR, and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14(+) monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time-dependent manner (superoxide: 0.9 ± 0.2 fold, 6 h vs. 3.0 ± 0.3 fold, 36 h; NE, 50 μg/ml; P < 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via α-adrenergic receptors, preferentially α2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor Staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14(+) monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through α-adrenergic receptors, an effect facilitating monocyte adhesion to the endothelium.
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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.