Evidence map›Paper›PMID 33970224›Full record

ArticleCardiovascular research2022

CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI: difference from BNP visualized by targeted cGMP biosensors.

Ornella Manfra, Gaia Calamera, Alexander Froese, Dulasi Arunthavarajah, Nicoletta C Surdo, Silja Meier, Arne Olav Melleby, Monica Aasrum, Jan Magnus Aronsen, Viacheslav O Nikolaev and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Sodium Alginate Attenuates HMolecular biotechnology · 2026
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  3. Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025
    Review
  4. Review
  5. Role of Phosphodiesterases in Biology and Pathology 2.0.International journal of molecular sciences · 2024
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease.International journal of molecular sciences · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 3 countries.

Ornella ManfraDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0002-3802-6690
Gaia CalameraDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0003-0689-8387
Alexander FroeseGerman Center for Cardiovascular Research, University Medical Center Hamburg-Eppendorf and Institute of Experimental Cardiovascular Research, Hamburg, Germany.
Dulasi ArunthavarajahDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0002-5931-697X
Nicoletta C SurdoDepartment of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.ORCID 0000-0001-8269-295X
Silja MeierDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.
Arne Olav MellebyDepartment of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.ORCID 0000-0002-3524-8829
Monica AasrumDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0003-3277-787X
Jan Magnus AronsenDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0003-2593-1744
Viacheslav O NikolaevGerman Center for Cardiovascular Research, University Medical Center Hamburg-Eppendorf and Institute of Experimental Cardiovascular Research, Hamburg, Germany.ORCID 0000-0002-7529-5179
Manuela ZaccoloDepartment of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.ORCID 0000-0002-0934-3662
Lise Román MoltzauDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0002-8041-147X
Finn Olav LevyDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0003-2564-6898
Kjetil Wessel AndressenDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, P.O. Box 1057 Blindern, 0316 Oslo, Norway.ORCID 0000-0003-1094-1501
Oslo University Hospital · NOUniversität Hamburg · DEUniversity of Oxford · GBUniversity of Oslo · NO

Funding

British Heart Foundation RG/17/6/32944
6 · The paper itself

Abstract

aimsGuanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes. METHODS AND

resultsWe constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (PLB) and troponin I (TnI). CNP stimulation of adult rat cardiomyocytes increased cGMP near PLB and TnI, whereas BNP stimulation increased cGMP near PLB, but not TnI. The phosphodiesterases PDE2 and PDE3 constrained cGMP in both compartments. Local receptor stimulation aided by scanning ion conductance microscopy (SICM) combined with FRET revealed that CNP stimulation both in the t-tubules and on the cell crest increases cGMP similarly near both TnI and PLB. In ventricular strips, CNP stimulation, but not BNP, induced a lusitropic response, enhanced by inhibition of either PDE2 or PDE3, and a negative inotropic response. In cardiomyocytes from heart failure rats, CNP increased cGMP near PLB and TnI more pronounced than in cells from sham-operated animals.

conclusionThese targeted biosensors demonstrate that CNP, but not BNP, increases cGMP near TnI in addition to PLB, explaining how CNP, but not BNP, is able to induce lusitropic and negative inotropic responses.

Indexed as

Biosensing TechniquesNatriuretic Peptide, BrainNatriuretic Peptide, C-TypeAnimalsAtrial Natriuretic FactorCyclic GMPEndoplasmic ReticulumGuanylate CyclaseMyocardial ContractionMyocytes, CardiacRatsReceptors, Atrial Natriuretic FactorTroponin IAtrial Natriuretic FactorCyclic GMPGuanylate CyclaseNatriuretic Peptide, BrainNatriuretic Peptide, C-TypeReceptors, Atrial Natriuretic FactorTroponin IAKAP18δBiosensorNatriuretic peptide receptorNPRPLN

Identifiers

PMID33970224
PMCPMC9074987
OpenAlexW3163748820

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.