ArticleAmerican journal of physiology. Heart and circulatory physiology2010
Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury.
Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease.British journal of pharmacology · 2020Review
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection.International journal of molecular sciences · 2019Review
- Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase.Scientific reports · 2019Article
- Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection?Heart (British Cardiac Society) · 2018Review
- Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality.Heart (British Cardiac Society) · 2016Observational
- 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
- Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.International journal of molecular sciences · 2015Article
- Investigation of therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in rat.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism.British journal of pharmacology · 2015Review
- Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil.Future cardiology · 2015Review
- Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats.PloS one · 2015Article
- Protein glutathionylation in cardiovascular diseases.International journal of molecular sciences · 2013Review
- Effectiveness and safety of phosphodiesterase 5 inhibitors in patients with cardiovascular disease and hypertension.Current hypertension reports · 2013Review
- Nitric oxide regulates cardiac intracellular Na⁺ and Ca²⁺ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.Journal of molecular and cellular cardiology · 2013Article
- Review
- Regulation of the cardiac sodium pump.Cellular and molecular life sciences : CMLS · 2013Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The phosphodiesterase type-5 inhibitor sildenafil has powerful cardioprotective effects against ischemia-reperfusion injury. PKG-mediated signaling has been implicated in this protection, although the mechanism and the downstream targets of this kinase remain to be fully elucidated. In this study we assessed the role of phospholemman (PLM) phosphorylation, which activates the Na(+)/K(+)-ATPase, in cardioprotection afforded by sildenafil administered during reperfusion. Isolated perfused mouse hearts were optimally protected against infarction (indexed by tetrazolium staining) by 0.1 muM sildenafil treatment during the first 10 min of reperfusion. Extended sildenafil treatment (30, 60, or 120 min at reperfusion) did not alter the degree of protection provided. This protection was PKG dependent, since it was blocked by KT-5823. Western blot analysis using phosphospecific antibodies to PLM showed that sildenafil at reperfusion did not modulate PLM Ser63 or Ser68 phosphorylation but significantly increased Ser69 phosphorylation. The treatment of isolated rat ventricular myocytes with sildenafil or 8-bromo-cGMP (PKG agonist) enhanced PLM Ser69 phosphorylation, which was bisindolylmaleimide (PKC inhibitor) sensitive. Patch-clamp studies showed that sildenafil treatment also activated the Na(+)/K(+)-ATPase, which is anticipated in light of PLM Ser69 phosphorylation. Na(+)/K(+)-ATPase activation during reperfusion would attenuate Na(+) overload at this time, providing a molecular explanation of how sildenafil guards against injury at this time. Indeed, using flame photometry and rubidium uptake into isolated mouse hearts, we found that sildenafil enhanced Na(+)/K(+)-ATPase activity during reperfusion. In this study we provide a molecular explanation of how sildenafil guards against myocardial injury during postischemic reperfusion.
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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.