Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition

Circulation
Toru HashimotoDavid A Kass

Abstract

Phosphodiesterase type-1 (PDE1) hydrolyzes cAMP and cGMP and is constitutively expressed in the heart, although cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly expresses PDE1C with balanced selectivity for cAMP and cGMP. Here, we determined the acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs, and rabbits, in normal and failing hearts, and explored its regulatory pathways. Conscious dogs chronically instrumented for pressure-volume relations were studied before and after tachypacing-induced heart failure (HF). A selective PDE1 inhibitor (ITI-214) was administered orally or intravenously±dobutamine. Pressure-volume analysis in anesthetized rabbits tested the role of β-adrenergic and adenosine receptor signaling on ITI-214 effects. Sarcomere and calcium dynamics were studied in rabbit left ventricular myocytes. In normal and HF dogs, ITI-214 increased load-independent contractility, improved relaxation, and reduced systemic arterial resistance, raising cardiac output without altering systolic blood pressure. Heart rate increased, but less so in HF dogs. ITI-214 effects were add...Continue Reading

References

Sep 14, 2006·Pharmacological Reviews·Andrew T Bender, Joseph A Beavo
Aug 30, 2007·The Journal of Biological Chemistry·Fabrice VandeputMatthew A Movsesian
Aug 17, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Carmen MethnerThomas Krieg
Oct 12, 2010·American Journal of Physiology. Heart and Circulatory Physiology·P Charukeshi ChandrasekeraRobert D Lasley
Jan 20, 2011·Basic Research in Cardiology·Karina GrubeThomas Krieg
Sep 20, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Oscar H Cingolani, David A Kass
Sep 29, 2011·Cellular and Molecular Life Sciences : CMLS·Manuel MorgadoIgnacio Verde
Jan 12, 2012·British Journal of Pharmacology·Paul A InselNakon Aroonsakool
Mar 13, 2013·JAMA : the Journal of the American Medical Association·Margaret M RedfieldUNKNOWN RELAX Trial
Jun 15, 2013·Pharmacology & Therapeutics·John P HeadrickJason N Peart
Jul 3, 2013·Journal of the American College of Cardiology·Hind MehelAli El-Armouche
Oct 11, 2013·Circulation. Heart Failure·Hani N SabbahDavid A Kass
Feb 5, 2014·Journal of the American College of Cardiology·Andrew P AmbrosyMihai Gheorghiade
Apr 2, 2014·Nature Reviews. Drug Discovery·Donald H MauriceVincent C Manganiello
Jun 7, 2014·Journal of the American Heart Association·Cristina E MolinaGrégoire Vandecasteele
Dec 3, 2014·Pharmacology & Therapeutics·Anindita DasRakesh C Kukreja
Jul 3, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seong-wook SeoTobias Eckle
Sep 5, 2015·Drugs·Karly P Garnock-Jones
Oct 21, 2015·Frontiers in Pharmacology·Cédric Boularan, Céline Gales
Mar 5, 2016·Circulation Research·Frank Lezoualc'hCaroline Conte
Apr 26, 2016·Pharmacology & Therapeutics·Matthew Movsesian
May 18, 2016·Archives of Cardiovascular Diseases·Pierre BobinGrégoire Vandecasteele
Jul 2, 2016·Journal of Molecular and Cellular Cardiology·Yevgeniya O LukyanenkoEdward G Lakatta
Oct 13, 2016·Annual Review of Pharmacology and Toxicology·Kristen Kokkonen, David A Kass
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Walter E KnightChen Yan
May 23, 2017·Cellular Signalling·Omar Torres-QuesadaEduard Stefan
May 23, 2017·Frontiers in Pharmacology·Elizabeth A VecchioLauren T May
Feb 9, 2018·Journal of Cardiovascular Development and Disease·Matthew MovsesianEmilio Hirsch

❮ Previous
Next ❯

Citations

Oct 30, 2018·Circulation·Jérôme Leroy, Rodolphe Fischmeister
May 24, 2019·Circulation Research·Miguel Pinilla-VeraDavid A Kass
Oct 28, 2019·Journal of Cardiovascular Pharmacology·Brittany Dunkerly-Eyring, David A Kass
Feb 11, 2020·Journal of Cardiovascular Pharmacology·Friederike Cuello, Viacheslav O Nikolaev
Sep 23, 2020·Expert Opinion on Drug Discovery·Si Chen, Chen Yan
Sep 10, 2019·Journal of Cardiovascular Pharmacology·Michael E J PreedyAdrian J Hobbs
Mar 17, 2020·Cardiovascular Drugs and Therapy·Michael E J Preedy
Aug 8, 2019·Nature Reviews. Drug Discovery·George S BaillieMichy P Kelly
Aug 28, 2020·Frontiers in Physiology·Christian U OeingMark J Ranek
Jan 8, 2021·European Journal of Medicinal Chemistry·Nathalia Fonseca NadurArthur Eugen Kümmerle
Nov 14, 2020·Journal of Molecular and Cellular Cardiology·Aniella Abi-GergesGrégoire Vandecasteele
Jan 24, 2021·Cardiovascular Research·Yuening LiuZhaokang Cheng
Jan 12, 2020·Pharmacology & Therapeutics·Claire LugnierBernard Geny
Jun 14, 2020·Current Topics in Medicinal Chemistry·Mayasah Y Al-Nema, Anand Gaurav
Nov 27, 2019·Molecular and Cellular Neurosciences·Jennifer J O'BrienJoseph P Hendrick
Apr 26, 2021·Pharmacology & Therapeutics·Arun SamiduraiRakesh C Kukreja
May 19, 2021·European Journal of Clinical Investigation·Dony YugoYi-Jen Chen
Jul 24, 2021·Progress in Biophysics and Molecular Biology·Delphine Mika, Rodolphe Fischmeister
Jun 9, 2021·The Journal of Pharmacology and Experimental Therapeutics·Keivan GolshiriAnton J M Roks
Sep 11, 2021·European Journal of Pharmacology·Hui-Wen YangHsiang-Yu Yang
Sep 16, 2021·Circulation Research·Grace K MullerDavid A Kass

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.