ArticleCardiovascular research2014
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect.
Article in Cardiovascular research, 2014. 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, 25 citations in OpenAlex.
- Stretch regulation of β2-Adrenoceptor signalling in cardiomyocytes requires caveolae.Cardiovascular research · 2025Article
- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- Caveolae-associated cAMP/CaJournal of molecular and cellular cardiology · 2023Article
- Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- Myocardial oedema: pathophysiological basis and implications for the failing heart.ESC heart failure · 2022Review
- Lung Cancer Induces NK Cell Contractility and Cytotoxicity Through Transcription Factor Nuclear Localization.Frontiers in cell and developmental biology · 2022Article
- Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G.Current research in physiology · 2022Article
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
- Muscarinic-dependent phosphorylation of the cardiac ryanodine receptor by protein kinase G is mediated by PI3K-AKT-nNOS signaling.The Journal of biological chemistry · 2020Article
- Nitric Oxide and Mechano-Electrical Transduction in Cardiomyocytes.Frontiers in physiology · 2020Review
- Alterations of tumor microenvironment by nitric oxide impedes castration-resistant prostate cancer growth.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- FK506-binding proteins 12 and 12.6 (FKBPs) as regulators of cardiac Ryanodine Receptors: Insights from new functional and structural knowledge.Channels (Austin, Tex.) · 2017Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsCardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. METHODS AND
resultsSuperfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca(2+) transient, and increased NO-sensitive 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor l-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either l-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca(2+) wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca(2+) release.
conclusionsOur findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling.
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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.