ArticleScientific reports2019
Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Natriuretic Peptides as Multisystem Regulators: From Clinical Biomarkers to Therapeutic Targets in Cardio-immunology.Cardiovascular drugs and therapy · 2026Review
- Evidence for the Additional Health Benefits Associated with Phosphodiesterase 5 Inhibitors when Used for Treating Erectile Dysfunction, with a Focus on Prostate Cancer Patients and Other Associated Conditions.The world journal of men's health · 2026Review
- Suppression of premature ventricular complexes with the PDE5 inhibitor sildenafil: First clinical experience.Experimental physiology · 2026Article
- Article
- Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.American journal of physiology. Heart and circulatory physiology · 2025Review
- A refined, minimally invasive, reproducible ovine ischaemia-reperfusion-infarction model using implantable defibrillators: Methodology and validation.Experimental physiology · 2025Article
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Enhanced CaJACC. Clinical electrophysiology · 2024Article
- Restoring Atrial T-Tubules Augments Systolic Ca Upon Recovery From Heart Failure.Circulation research · 2024Article
- Interaction of background CaThe Journal of physiology · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- PDE5 Inhibition Suppresses Ventricular Arrhythmias by Reducing SR CaCirculation research · 2021Article
- Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure.International journal of molecular sciences · 2021Review
- Protective Effects ofFrontiers in pharmacology · 2021Review
- The Physiology and Pathophysiology of T-Tubules in the Heart.Frontiers in physiology · 2021Review
- Myocardial Impact of NHE1 Regulation by Sildenafil.Frontiers in cardiovascular medicine · 2021Review
- Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension.International journal of molecular sciences · 2020Review
- Postimplant Phosphodiesterase Type 5 Inhibitors Use Is Associated With Lower Rates of Thrombotic Events After Left Ventricular Assist Device Implantation.Journal of the American Heart Association · 2020Article
- Sildenafil Recovers Burn-Induced Cardiomyopathy.Cells · 2020Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction. Using a sheep model of advanced HF, we show that tadalafil treatment improves contractile function, reverses transverse tubule loss, restores calcium transient amplitude and the heart's response to catecholamines. Accompanying these effects, tadalafil treatment normalized BNP mRNA and prevented development of subjective signs of HF. These effects were independent of changes in myocardial cGMP content and were associated with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 and 3. We propose that the molecular switch for the loss of transverse tubules in HF and their restoration following tadalafil treatment involves the BAR domain protein Amphiphysin II (BIN1) and the restoration of catecholamine sensitivity is through reductions in G-protein receptor kinase 2, protein phosphatase 1 and protein phosphatase 2 A abundance following phosphodiesterase 5 inhibition.
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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.