ArticleCirculation research1999
Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes.
Article in Circulation research, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 272 citations in OpenAlex.
- Influence of Soluble Guanylate Cyclase on Cardiac, Vascular, and Renal Structure and Function: A Physiopathological Insight.International journal of molecular sciences · 2025Review
- Cardiovascular Disease in HIV Patients: A Comprehensive Review of Current Knowledge and Clinical Implications.International journal of molecular sciences · 2025Review
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles.Frontiers in pharmacology · 2024Review
- The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytes.Physiological reports · 2022Article
- Carbon monoxide activation of delayed rectifier potassium currents of human cardiac fibroblasts through diverse pathways.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G.Current research in physiology · 2022Article
- Identification of genes associated with sudden cardiac death: a network- and pathway-based approach.Journal of thoracic disease · 2021Article
- Sweat the small stuff: The human microvasculature and heart disease.Microcirculation (New York, N.Y. : 1994) · 2021Review
- Electrophysiological and Molecular Mechanisms of Sinoatrial Node Mechanosensitivity.Frontiers in cardiovascular medicine · 2021Article
- Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.Advances in experimental medicine and biology · 2021Review
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- Nitric Oxide and Mechano-Electrical Transduction in Cardiomyocytes.Frontiers in physiology · 2020Review
- A Nitric Oxide-Dependent Presynaptic LTP at Glutamatergic Synapses of the PVN Magnocellular Neurosecretory CellsFrontiers in cellular neuroscience · 2019Article
- Effects of Nitric Oxide on Voltage-Gated K⁺ Currents in Human Cardiac Fibroblasts through the Protein Kinase G and Protein Kinase A Pathways but Not through S-Nitrosylation.International journal of molecular sciences · 2018Article
- Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling.Circulation research · 2018Review
- Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network.Journal of molecular and cellular cardiology · 2016Article
- Interaction of Hydrogen Sulfide with Nitric Oxide in the Cardiovascular System.Oxidative medicine and cellular longevity · 2016Review
- Breakthrough in heart failure with preserved ejection fraction: are we there yet?The Korean journal of internal medicine · 2016Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Nitric oxide (NO) donors were recently shown to produce biphasic contractile effects in cardiac tissue, with augmentation at low NO levels and depression at high NO levels. We examined the subcellular mechanisms involved in the opposing effects of NO on cardiac contraction and investigated whether NO modulates contraction exclusively via guanylyl cyclase (GC) activation or whether some contribution occurs via cGMP/PKG-independent mechanisms, in indo 1-loaded adult cardiac myocytes. Whereas a high concentration of the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 micromol/L) significantly attenuated contraction amplitude by 24.4+/-4.5% (without changing the Ca2+ transient or total cAMP), a low concentration of SNAP (1 micromol/L) significantly increased contraction amplitude (38+/-10%), Ca2+ transient (26+/-10%), and cAMP levels (from 6.2 to 8.5 pmol/mg of protein). The negative contractile response of 100 micromol/L SNAP was completely abolished in the presence of the specific blocker of PKG KT 5823 (1 micromol/L); the positive contractile response of 1 micromol/L SNAP persisted, despite the presence of the selective inhibitor of GC 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 micromol/L) alone, but was completely abolished in the presence of ODQ plus the specific inhibitory cAMP analog Rp-8-CPT-cAMPS (100 micromol/L), as well as by the NO scavenger oxyhemoglobin. Parallel experiments in cell suspensions showed significant increases in adenylyl cyclase (AC) activity at low concentrations (0.1 to 1 micromol/L) of SNAP (AC, 18% to 20% above basal activity). We conclude that NO can regulate both AC and GC in cardiac myocytes. High levels of NO induce large increases in cGMP and a negative inotropic effect mediated by a PKG-dependent reduction in myofilament responsiveness to Ca2+. Low levels of NO increase cAMP, at least in part, by a novel cGMP-independent activation of AC and induce a positive contractile response.
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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.