ArticleCirculation2009
Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Pre- and postconditioning the heart with hydrogen sulfide (HBasic research in cardiology · 2018Pooled it
- Effects of tadalafil administration on plasma markers of exercise-induced muscle damage, IL6 and antioxidant status capacity.European journal of applied physiology · 2015Trial
- Mitochondrial potassium channels: mitochondria-specific mechanism of regulation.Biophysical reviews · 2026Review
- Serum Galectin-3 and Risk Stratification in Chronic Heart Failure: A Systematic Review of Mortality Outcomes.Cureus · 2025Review
- Comparison of plasma metabolic profiling between children with hypertrophic obstructive cardiomyopathy and healthy controls.Cardiovascular endocrinology & metabolism · 2025Article
- Hydrogen sulfide maintains mitochondrial homeostasis and regulates ganoderic acids biosynthesis by SQR under heat stress in Ganoderma lucidum.Redox biology · 2024Article
- Hydrogen sulfide and its potential as a possible therapeutic agent in male reproduction.Frontiers in endocrinology · 2024Review
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.Cardiovascular drugs and therapy · 2023Review
- Phosphodiesterase-5 Inhibitors as Therapeutics for Cardiovascular Diseases: A Brief Review.Iranian journal of public health · 2023Review
- Treating diabetes with combination of phosphodiesterase 5 inhibitors and hydroxychloroquine-a possible prevention strategy for COVID-19?Molecular and cellular biochemistry · 2023Review
- Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.Pharmacology & therapeutics · 2021Review
- Effect of Tadalafil Administration on Redox Homeostasis and Polyamine Levels in Healthy Men with High Level of Physical Activity.International journal of environmental research and public health · 2021Article
- MTORC1-Regulated Metabolism Controlled by TSC2 Limits Cardiac Reperfusion Injury.Circulation research · 2021Article
- Garlic Derived Diallyl Trisulfide in Experimental Metabolic Syndrome: Metabolic Effects and Cardioprotective Role.International journal of molecular sciences · 2020Article
- Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease.Mechanisms of ageing and development · 2020Review
- PDE5 inhibitor sildenafil attenuates cardiac microRNA 214 upregulation and pro-apoptotic signaling after chronic alcohol ingestion in mice.Molecular and cellular biochemistry · 2020Article
- Osteocrin attenuates inflammation, oxidative stress, apoptosis, and cardiac dysfunction in doxorubicin-induced cardiotoxicity.Clinical and translational medicine · 2020Article
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- Chronic inhibition of phosphodiesterase 5 with tadalafil affords cardioprotection in a mouse model of metabolic syndrome: role of nitric oxide.Molecular and cellular biochemistry · 2020Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTadalafil is a novel long-acting inhibitor of phosphodiesterase-5. Because cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that PKG activation with tadalafil would limit myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide (H(2)S) signaling in a PKG-dependent fashion. METHODS AND
resultsAfter baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine (PAG, Cystathionine-gamma-lyase [CSE, H(2)S-producing enzyme] blocker; 50 mg/kg) 1 hour before coronary artery ligation for 30 minutes and reperfusion for 24 hours, whereas C57BL wild-type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2+/-1.7%) compared to vehicle (40.6+/-2.5%; P<0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2+/-1% and 51.2+/-2.4%, respectively) similar to genetic deletion of CSE (47.2+/-5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31+/-1.5%) compared to control (FS: 22+/-4.8%, P<0.05). Baseline FS was 44+/-1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by decline in FS to 17+/-1% and 23+/-3%, respectively. Compared to vehicle, myocardial H(2)S production was significantly increased with tadalafil and was abolished with KT.
conclusionsPKG activation with tadalafil limits myocardial infarction and preserves LV function through H(2)S signaling.
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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.