title: PDE3 inhibition in dilated cardiomyopathy.
abstract: In dilated cardiomyopathy, a condition characterized by chamber enlargement and reduced myocardial contractility, decreases in β-adrenergic receptor density and increases in Gαi and β-adrenergic receptor kinase activities attenuate the stimulation of adenylyl cyclase in response to catecholamines. PDE3 inhibitors have been used to 'overcome' the reduction in cAMP generation by blocking cAMP hydrolysis. These drugs increase contractility in the short-term, but long-term administration leads to an increase in mortality that correlates with an increase in sudden cardiac death. Whether separate mechanisms account for these beneficial and harmful effects, and, if so, whether PDE3 can be targeted so as to increase contractility without increasing mortality are questions that remain unanswered.
authors.affiliation: Cardiology Section, VA Salt Lake City Health Care System, and Departments of Internal Medicine (Cardiology) and Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, USA. matthew.movsesian@va.gov
authors.forename: Matthew
authors.initials: M
authors.lastname: Movsesian
authors.forename: Omar
authors.initials: O
authors.lastname: Wever-Pinzon
authors.forename: Fabrice
authors.initials: F
authors.lastname: Vandeput
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000502:physiology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000737:chemistry / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D058987:Phosphodiesterase 3 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015290:Second Messenger Systems / Q000187:drug effects
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D000242:Cyclic AMP; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3