ArticleBMC pharmacology2005
Sildenafil citrate increases myocardial cGMP content in rat heart, decreases its hypertrophic response to isoproterenol and decreases myocardial leak of creatine kinase and troponin T.
Article in BMC pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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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Who cites it
19 citing papers in PubMed, 58 citations in OpenAlex.
- Trial
- Sildenafil-Induced Revascularization of Rat Hindlimb Involves Arteriogenesis through PI3K/AKT and eNOS Activation.International journal of molecular sciences · 2022Article
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension.Scientific reports · 2019Article
- The Effect of Sorafenib, Tadalafil and Macitentan Treatments on Thyroxin-Induced Hemodynamic Changes and Cardiac Abnormalities.PloS one · 2016Article
- Therapeutic effects of udenafil on pressure-overload cardiac hypertrophy.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Article
- Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis through inhibition of transforming growth factor β-induced Smad signaling.Frontiers of medicine · 2014Article
- Clinical and molecular genetics of the phosphodiesterases (PDEs).Endocrine reviews · 2014Review
- The role of sulfur dioxide in the regulation of mitochondrion-related cardiomyocyte apoptosis in rats with isopropylarterenol-induced myocardial injury.International journal of molecular sciences · 2013Article
- Differential expression of PDE5 in failing and nonfailing human myocardium.Circulation. Heart failure · 2012Article
- Article
- KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways.British journal of pharmacology · 2010Article
- Phosphodiesterase inhibition in heart failure.Heart failure reviews · 2009Review
- cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium.The Journal of pharmacology and experimental therapeutics · 2009Article
- Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1.Journal of cellular and molecular medicine · 2008Article
- Sildenafil and phosphodiesterase-5 inhibitors for heart failure.Current heart failure reports · 2008Review
- Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat.British journal of pharmacology · 2007Article
- Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond.Nature reviews. Drug discovery · 2006Review
- Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study.Brazilian journal of anesthesiology (Elsevier)Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiac hypertrophy is a major risk factor for morbidity and mortality in a number of cardiovascular diseases. Consequently, the signaling pathways that inhibit cardiac hypertrophy are currently receiving much interest. Among them, nitric oxide (NO), signaling via cGMP and cGMP-dependent protein kinase I, has been recognized as a negative regulator of cardiac hypertrophy. The present study investigated the in-vivo effect of sildenafil as a phosphodiestrase-5A (PDE-5A) inhibitor on the hypertrophic response of rat heart to isoproterenol and the relation of this effect to the level of myocardial cGMP and integrity of the constitutive nitric oxide synthase (cNOS) activity.
resultsThe results showed that daily intraperitoneal administration of sildenafil per se for 10 days was without noticeable adverse effects on survival or myocardium. Conversely, daily subcutaneous administration of isoproterenol for 10 days caused significant myocardial hypertrophy, cell injury and decline in survival. When sildenafil was injected daily, one hour before isoproterenol, survival was significantly improved and the myocardium didn't show significant hypertrophy or cell injury. Interestingly, sildenafil was accompanied by significant rise in myocardial cGMP level, a parameter which was found in the present study to possess a significant negative correlation with cardiac hypertrophy and leak of cardiac troponin T into serum. At the same time, cGMP was found to possess a positive correlation with myocardial creatine kinase activity that reflects the efficiency of the energy utilization processes in the myocardium. However, in rats given Nomega-nitro-L-arginine (L-NNA) as a competitive inhibitor of cNOS, sildenafil failed to show any favorable effect on survival or the myocardial injury parameters used to assess isoproterenol-induced injury.
conclusionThe present study suggests that increased cardiac cGMP level by sildenafil have a cardioprotective effect probably through acting as a post-receptor negative regulator of cardiac sympathetic responsiveness. Integrity of NOS function was an essential prerequisite for sildenafil's mediated cardioprotection encountered in the present study.
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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 Socratic graph.