ArticleBritish journal of pharmacology2009
Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial K(ATP) channel.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Effect of intravenous levosimendan or milrinone on left atrial pressure in patients undergoing off-pump coronary artery bypass grafting-A prospective double-blind, randomized controlled trial.Annals of cardiac anaesthesiaTrial
- Prophylactic preoperative levosimendan for off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: Single-centered randomized prospective study.Annals of cardiac anaesthesiaTrial
- Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes.Journal of clinical medicine · 2024Article
- An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer.Current issues in molecular biology · 2024Article
- Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling.Biomedicines · 2024Article
- Levosimendan, a Promising Pharmacotherapy in Cardiogenic Shock: A Comprehensive Review.European cardiology · 2024Review
- Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.Biomolecules · 2023Review
- The Effects of the Levosimendan Metabolites OR-1855 and OR-1896 on Endothelial Pro-Inflammatory Responses.Biomedicines · 2023Article
- Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study.Life (Basel, Switzerland) · 2022Article
- The Adenylate Cyclase Activator Forskolin Potentiates the Positive Inotropic Effect of the Phosphodiesterase Inhibitor Milrinone But Not of the Calcium Sensitizer Levosimendan nor of Its Hemodynamically Active Metabolites: An Apparent Conundrum.Journal of cardiovascular pharmacology · 2022Article
- Levosimendan-induced venodilation is mediated by opening of potassium channels.ESC heart failure · 2021Review
- Levosimendan in Europe and China: An Appraisal of Evidence and Context.European cardiology · 2021Review
- Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle.Frontiers in physiology · 2021Article
- Postoperative Atrial Fibrillation Following Cardiac Surgery: From Pathogenesis to Potential Therapies.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Review
- Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the KAmerican journal of physiology. Cell physiology · 2019Article
- Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets.International journal of molecular sciences · 2019Review
- Levosimendan as a new force in the treatment of sepsis-induced cardiomyopathy: mechanism and clinical application.The Journal of international medical research · 2019Review
- Impact of levosimendan on weaning from peripheral venoarterial extracorporeal membrane oxygenation in intensive care unit.Annals of intensive care · 2019Article
- Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy.International journal of molecular medicine · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLevosimendan acts as a vasodilator through the opening of ATP-sensitive K(+) channels (K(ATP)) channels. Moreover, the coronary vasodilatation caused by levosimendan in anaesthetized pigs has recently been found to be abolished by the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the vascular effects of levosimendan. However, the intracellular pathway leading to NO production caused by levosimendan has not yet been investigated. Thus, the purpose of the present study was to examine the effects of levosimendan on NO production and to evaluate the intracellular signalling pathway involved. EXPERIMENTAL APPROACH: In porcine coronary endothelial cells (CEC), the release of NO in response to levosimendan was examined in the presence and absence of N(omega)-nitro-L-arginine methyl ester, an adenylyl cyclase inhibitor, K(ATP) channel agonists and antagonists, and inhibitors of intracellular protein kinases. In addition, the role of Akt, ERK, p38 and eNOS was investigated through Western blot analysis. KEY
resultsLevosimendan caused a concentration-dependent and K(+)-related increase of NO production. This effect was amplified by the mitochondrial K(ATP) channel agonist, but not by the selective plasma membrane K(ATP) channel agonist. The response of CEC to levosimendan was prevented by the K(ATP) channel blockers, the adenylyl cyclase inhibitor and the Akt, ERK, p38 inhibitors. Western blot analysis showed that phosphorylation of the above kinases lead to eNOS activation. CONCLUSIONS AND IMPLICATIONS: In CEC levosimendan induced eNOS-dependent NO production through Akt, ERK and p38. This intracellular pathway is associated with the opening of mitochondrial K(ATP) channels and involves cAMP.
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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.