ArticleBMC pharmacology & toxicology2013
The favorable kinetics and balance of nebivolol-stimulated nitric oxide and peroxynitrite release in human endothelial cells.
Article in BMC pharmacology & toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Effect of nebivolol or atenolol vs. placebo on cardiovascular health in subjects with borderline blood pressure: the EVIDENCE study.Journal of human hypertension · 2017Trial
- Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol.Journal of clinical hypertension (Greenwich, Conn.) · 2016Trial
- Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension.British journal of clinical pharmacology · 2015Trial
- Cardiovascular β-Adrenergic Receptor Distribution and Function: Influence of Species, Sex, Age, and Tissue.Comprehensive Physiology · 2026Review
- Carvedilol induces biased β1 adrenergic receptor-nitric oxide synthase 3-cyclic guanylyl monophosphate signalling to promote cardiac contractility.Cardiovascular research · 2021Article
- Article
- Tyrosine Kinase Inhibitor-Induced Hypertension.Current oncology reports · 2018Review
- Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin DInternational journal of nanomedicine · 2018Article
- Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β-Blockers?Journal of clinical hypertension (Greenwich, Conn.) · 2016Article
- Nebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis.Oncotarget · 2016Article
- Clinical Significance of Endothelial Dysfunction in Essential Hypertension.Current hypertension reports · 2015Review
- The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment.Frontiers in cardiovascular medicine · 2015Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNebivolol is a third-generation beta-blocker used to treat hypertension. The vasodilation properties of nebivolol have been attributed to nitric oxide (NO) release. However, the kinetics and mechanism of nebivolol-stimulated bioavailable NO are not fully understood.
methodsUsing amperometric NO and peroxynitrite (ONOO⁻) nanosensors, β₃-receptor (agonist: L-755,507; antagonists: SR59230A and L-748,337), ATP efflux (the mechanosensitive ATP channel blocker, gadolinium) and P2Y-receptor (agonists: ATP and 2-MeSATP; antagonist: suramin) modulators, superoxide dismutase and a NADPH oxidase inhibitor (VAS2870), we evaluated the kinetics and balance of NO and ONOO⁻ stimulated by nebivolol in human umbilical vein endothelial cells (HUVECs). NO and ONOO⁻ were measured with nanosensors (diameter ~ 300 nm) placed 5 ± 2 μm from the cell membrane and ATP levels were determined with a bioluminescent method. The kinetics and balance of nebivolol-stimulated NO and ONOO⁻ were compared with those of ATP, 2-MeSATP, and L-755,507.
resultsNebivolol stimulates endothelial NO release through β₃-receptor and ATP-dependent, P2Y-receptor activation with relatively slow kinetics (75 ± 5 nM/s) as compared to the kinetics of ATP (194 ± 10 nM/s), L-755,507 (108 ± 6 nM/s), and 2-MeSATP (105 ± 5 nM/s). The balance between cytoprotective NO and cytotoxic ONOO- was expressed as the ratio of [NO]/[ONOO⁻] concentrations. This ratio for nebivolol was 1.80 ± 0.10 and significantly higher than that for ATP (0.80 ± 0.08), L-755,507 (1.08 ± 0.08), and 2-MeSATP (1.09 ± 0.09). Nebivolol induced ATP release in a concentration-dependent manner.
conclusionThe two major pathways (ATP efflux/P2Y receptors and β₃ receptors) and several steps of nebivolol-induced NO and ONOO⁻ stimulation are mainly responsible for the slow kinetics of NO release and low ONOO⁻. The net effect of this slow kinetics of NO is reflected by a favorable high ratio of [NO]/[ONOO⁻] which may explain the beneficial effects of nebivolol in the treatment of endothelial dysfunction, hypertension, heart failure, and angiogenesis.
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