ArticlePloS one2013
Levosimendan Relaxes Pulmonary Arteries and Veins in Precision-Cut Lung Slices - The Role of KATP-Channels, cAMP and cGMP.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 34 citations in OpenAlex.
- Milrinone relaxes pulmonary veins in guinea pigs and humans.PloS one · 2014Trial
- Insights from precision-cut lung slices-investigating mechanisms and therapeutics for pulmonary hypertension.Respiratory research · 2025Review
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.Biomolecules · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Overexpression of GRK2 in vascular smooth muscle leads to inappropriate hypertension and acute heart failure as in clinical scenario 1.Scientific reports · 2023Article
- Functional changes in long-term incubated rat precision-cut lung slices.Respiratory research · 2022Article
- Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and CaRespiratory research · 2022Article
- Levosimendan-induced venodilation is mediated by opening of potassium channels.ESC heart failure · 2021Review
- Levosimendan reduces segmental pulmonary vascular resistance in isolated perfused rat lungs and relaxes human pulmonary vessels.PloS one · 2020Article
- The effects of oxygen concentration on cell death, anti-oxidant transcription, acute inflammation, and cell proliferation in precision-cut lung slices.Scientific reports · 2019Article
- Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.Respiratory research · 2019Article
- Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation.Scientific reports · 2019Article
- PDGF-BB regulates the pulmonary vascular tone: impact of prostaglandins, calcium, MAPK- and PI3K/AKT/mTOR signalling and actin polymerisation in pulmonary veins of guinea pigs.Respiratory research · 2018Article
- Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth.PloS one · 2018Article
- Imatinib relaxes the pulmonary venous bed of guinea pigs.Respiratory research · 2017Article
- Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review.Experimental and therapeutic medicine · 2016Article
- Inotropes and inodilators for acute heart failure: sarcomere active drugs in focus.Journal of cardiovascular pharmacology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionLevosimendan is approved for left heart failure and is also used in right heart failure to reduce right ventricular afterload. Despite the fact that pulmonary arteries (PAs) and pulmonary veins (PVs) contribute to cardiac load, their responses to levosimendan are largely unknown. MATERIALS AND
methodsLevosimendan-induced vasorelaxation of PAs and PVs was studied in precision-cut lung slices from guinea pigs by videomicroscopy; baseline luminal area was defined as 100%. Intracellular cAMP- and cGMP-levels were measured by ELISA and NO end products were determined by the Griess reaction.
resultsLevosimendan relaxed control PVs (116%) and those pre-constricted with an endothelinA-receptor agonist (119%). PAs were only relaxed if pre-constricted (115%). Inhibition of KATP-channels (glibenclamide), adenyl cyclase (SQ 22536) and protein kinase G (KT 5823) largely attenuated the levosimendan-induced relaxation in control PVs, as well as in pre-constricted PAs and PVs. Inhibition of BKCa (2+)-channels (iberiotoxin) and Kv-channels (4-aminopyridine) only contributed to the relaxant effect of levosimendan in pre-constricted PAs. In both PAs and PVs, levosimendan increased intracellular cAMP- and cGMP-levels, whereas NO end products remained unchanged. Notably, basal NO-levels were higher in PVs. The KATP-channel activator levcromakalim relaxed PAs dependent on cAMP/PKA/PKG and increased cAMP-levels in PAs. DISCUSSION: Levosimendan initiates complex and divergent signaling pathways in PAs and PVs. Levosimendan relaxes PAs and PVs primarily via KATP-channels and cAMP/cGMP; in PAs, BKCa (2+)- and Kv-channels are also involved. Our findings with levcromakalim do further suggest that in PAs the activation of KATP-channels leads to the production of cAMP/PKA/PKG. In conclusion, these results suggest that levosimendan might reduce right ventricular afterload by relaxation of PAs as well as pulmonary hydrostatic pressure and pulmonary edema by relaxation of PVs.
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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.