ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Endothelial nitric oxide synthase decreases beta-adrenergic responsiveness via inhibition of the L-type Ca2+ current.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
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- Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Nitric Oxide in Cardiac Surgery: A Review Article.Biomedicines · 2023Review
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- Bidirectional regulatory effects of Cordyceps on arrhythmia: Clinical evaluations and network pharmacology.Frontiers in pharmacology · 2022Article
- Ventricular arrhythmias in mouse models of diabetic kidney disease.Scientific reports · 2021Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Arrhythmogenic Mechanisms in Heart Failure: Linking β-Adrenergic Stimulation, Stretch, and Calcium.Frontiers in physiology · 2018Review
- Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity.American journal of physiology. Heart and circulatory physiology · 2017Article
- Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.Journal of molecular and cellular cardiology · 2017Article
- Nitric oxide: what's new to NO?American journal of physiology. Cell physiology · 2017Review
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- Cardioprotective Action ofFrontiers in pharmacology · 2017Article
- CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction-A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat.Frontiers in physiology · 2017Article
- The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio).Brain sciences · 2016Article
- Article
- Mechanisms of sudden cardiac death: oxidants and metabolism.Circulation research · 2015Review
- Defining the role of oxidative stress in atrial fibrillation and diabetes.Journal of cardiovascular electrophysiology · 2015Article
- Nitric Oxide Protects L-Type Calcium Channel of Cardiomyocyte during Long-Term Isoproterenol Stimulation in Tail-Suspended Rats.BioMed research international · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Signaling via endothelial nitric oxide synthase (NOS3) limits the heart's response to beta-adrenergic (beta-AR) stimulation, which may be protective against arrhythmias. However, mechanistic data are limited. Therefore, we performed simultaneous measurements of action potential (AP, using patch clamp), Ca2+ transients (fluo 4), and myocyte shortening (edge detection). L-type Ca2+ current (ICa) was directly measured by the whole cell ruptured patch-clamp technique. Myocytes were isolated from wild-type (WT) and NOS3 knockout (NOS3-/-) mice. NOS3-/- myocytes exhibited a larger incidence of beta-AR (isoproterenol, 1 microM)-induced early afterdepolarizations (EADs) and spontaneous activity (defined as aftercontractions). We also examined ICa, a major trigger for EADs. NOS3-/- myocytes had a significantly larger beta-AR-stimulated increase in ICa compared with WT myocytes. In addition, NOS3-/- myocytes had a larger response to beta-AR stimulation compared with WT myocytes in Ca2+ transient amplitude, shortening amplitude, and AP duration (APD). We observed similar effects with specific NOS3 inhibition [L-N5-(1-iminoethyl)-ornithine (l-NIO), 10 microM] in WT myocytes as with NOS3 knockout. Specifically, l-NIO further increased isoproterenol-stimulated EADs and aftercontractions. l-NIO also further increased the isoproterenol-stimulated ICa, Ca2+ transient amplitude, shortening amplitude, and APD (all P < 0.05 vs isoproterenol alone). l-NIO had no effect in NOS3-/- myocytes. These results indicate that NOS3 signaling inhibits the beta-AR response by reducing ICa and protects against arrhythmias. This mechanism may play an important role in heart failure, where arrhythmias are increased and NOS3 expression is decreased.
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