ArticleThe Journal of pharmacology and experimental therapeutics2009
cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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, 64 citations in OpenAlex.
- Exploratory research on drugs after lung surgery based on real-world data from the FDA adverse event reporting system database.PloS one · 2026Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension: Focus on Phosphodiesterase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from theInternational journal of molecular sciences · 2020Article
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- Phosphodiesterase-5 Is Elevated in Failing Single Ventricle Myocardium and Affects Cardiomyocyte Remodeling In Vitro.Circulation. Heart failure · 2018Article
- Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/reperfusion injury and for treating heart failure.British journal of pharmacology · 2018Review
- A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil.International journal of molecular sciences · 2017Article
- Chemotherapeutic efficacy of phosphodiesterase inhibitors in chagasic cardiomyopathy.JACC. Basic to translational science · 2016Article
- Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work?Journal of endocrinological investigation · 2016Review
- Right ventricular cyclic nucleotide signaling is decreased in hyperoxia-induced pulmonary hypertension in neonatal mice.American journal of physiology. Heart and circulatory physiology · 2015Article
- PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer.Pharmacology & therapeutics · 2015Review
- The emperor's new clothes: PDE5 and the heart.PloS one · 2015Article
- Age-related differences in phosphodiesterase activity and effects of chronic phosphodiesterase inhibition in idiopathic dilated cardiomyopathy.Circulation. Heart failure · 2015Article
- Exercise training in adverse cardiac remodeling.Pflugers Archiv : European journal of physiology · 2014Review
- Differential regulation of C-type natriuretic peptide-induced cGMP and functional responses by PDE2 and PDE3 in failing myocardium.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Selective regulation of cyclic nucleotide phosphodiesterase PDE3A isoforms.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Therapeutic potential of PDE modulation in treating heart disease.Future medicinal chemistry · 2013Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
In mouse models of cardiac disease, the type 5 (PDE5)-selective cyclic nucleotide phosphodiesterase inhibitor sildenafil has antihypertrophic and cardioprotective effects attributable to the inhibition of cGMP hydrolysis. To investigate the relevance of these findings to humans, we quantified cGMP-hydrolytic activity and its inhibition by sildenafil in cytosolic and microsomal preparations from the left ventricular myocardium of normal and failing human hearts. The vast majority of cGMP-hydrolytic activity was attributable to PDE1 and PDE3. Sildenafil had no measurable effect on cGMP hydrolysis at 10 nM, at which it is selective for PDE5, but it had a marked effect on cGMP and cAMP hydrolysis at 1 microM, at which it inhibits PDE1. In contrast, in preparations from the left ventricles of normal mice and mice with heart failure resulting from coronary artery ligation, the effects of sildenafil on cGMP hydrolysis were attributable to inhibition of both PDE5 and PDE1; PDE5 comprised approximately 22 and approximately 43% of the cytosolic cGMP-hydrolytic activity in preparations from normal and failing mouse hearts, respectively. These differences in PDE5 activities in human and mouse hearts call into question the extent to which the effects of sildenafil in mouse models are likely to be applicable in humans and raise the possibility of PDE1 as an alternative therapeutic target.
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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.