ArticleJournal of molecular and cellular cardiology2009
Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- sGC stimulator (BAY 41-8543) combined with PDE9 inhibitor (BAY 73-6691) reduces renal fibrosis in 5/6 nephrectomized rats.Basic & clinical pharmacology & toxicology · 2025Article
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.PloS one · 2024Article
- YC-1 induces GBioMedicine · 2017Article
- Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.Journal of molecular and cellular cardiology · 2017Article
- Article
- Abnormal Ca(2+) cycling in failing ventricular myocytes: role of NOS1-mediated nitroso-redox balance.Antioxidants & redox signaling · 2014Review
- Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension.European journal of clinical pharmacology · 2014Article
- Moving into a new neighborhood: NOS goes nuclear.Journal of molecular and cellular cardiology · 2013Article
- Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- Nitric oxide synthases in heart failure.Antioxidants & redox signaling · 2013Review
- cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function.Nature medicine · 2012Article
- Modulation of myocardial contraction by peroxynitrite.Frontiers in physiology · 2012Article
- Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes.Journal of signal transduction · 2012Article
- Agents increasing cyclic GMP amplify 5-HT4-elicited positive inotropic response in failing rat cardiac ventricle.Naunyn-Schmiedeberg's archives of pharmacology · 2011Article
- sGC{alpha}1 mediates the negative inotropic effects of NO in cardiac myocytes independent of changes in calcium handling.American journal of physiology. Heart and circulatory physiology · 2011Article
- Phosphodiesterases and cardiac cGMP: evolving roles and controversies.Trends in pharmacological sciences · 2011Review
- Roles of the nitric oxide signaling pathway in cardiac ischemic preconditioning against myocardial ischemia-reperfusion injury.Medical science monitor : international medical journal of experimental and clinical research · 2011Review
- cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action.Pharmacological reviews · 2010Review
- PDE5A suppression of acute beta-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation.Basic research in cardiology · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial nitric oxide synthase (NOS3) regulates the functional response to beta-adrenergic (beta-AR) stimulation via modulation of the L-type Ca(2+) current (I(Ca)). However, the NOS3 signaling pathway modulating I(Ca) is unknown. This study investigated the contribution of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5), a cGMP-specific PDE, in the NOS3-mediated regulation of I(Ca). Myocytes were isolated from NOS3 knockout (NOS3(-/-)) and wildtype (WT) mice. We measured I(Ca) (whole-cell voltage-clamp), and simultaneously measured Ca(2+) transients (Fluo-4 AM) and cell shortening (edge detection). Zaprinast (selective inhibitor of PDE5), decreased beta-AR stimulated (isoproterenol, ISO)-I(Ca), and Ca(2+) transient and cell shortening amplitudes in WT myocytes. However, YC-1 (NO-independent activator of sGC) only reduced ISO-stimulated I(Ca), but not cardiac contraction. We further investigated the NOS3/sGC/PDE5 pathway in NOS3(-/-) myocytes. PDE5 is mislocalized in these myocytes and we observed dissimilar effects of PDE5 inhibition and sGC activation compared to WT. That is, zaprinast had no effect on ISO-stimulated I(Ca), or Ca(2+) transient and cell shortening amplitudes. Conversely, YC-1 significantly decreased both ISO-stimulated I(Ca), and cardiac contraction. Further confirming that PDE5 localizes NOS3/cGMP signaling to I(Ca); YC-1, in the presence of zaprinast, now significantly decreased ISO-stimulated Ca(2+) transient and cell shortening amplitudes in WT myocytes. The effects of YC-1 on I(Ca) and cardiac contraction were blocked by KT5823 (a selective inhibitor of the cGMP-dependent protein kinase, PKG). Our data suggests a novel physiological role for PDE5 in restricting the effects of NOS3/sGC/PKG signaling pathway to modulating beta-AR stimulated I(Ca), while limiting effects on cardiac contraction.
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