Phosphodiesterase 5 inhibition in heart failure: mechanisms and clinical implications.
Phosphodiesterase 5 (PDE5) selectively hydrolyzes cyclic guanosine monophosphate. Inhibitors of PDE5 were originally developed to treat angina pectoris, and currently have multiple therapeutic indications, including erectile dysfunction and pulmonary hypertension. Several lines of research have provided evidence to support various potential PDE5-dependent cellular mechanisms in the myocardium that are involved in the pathophysiology of heart failure and cardiac dysfunction. In this Review we provide a mechanistic overview of the pharmacological inhibition of PDE5 in the context of heart failure, and evaluate the evidence supporting the use of novel PDE5 inhibitors in the treatment of this condition.
Kumar
Praneet
P
Cleveland Clinic, Cleveland, OH 44195, USA.
Francis
Gary S
GS
Tang
W H Wilson
WH
D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009206:Myocardium / Q000201:enzymology*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000187:drug effects
D002317:Cardiovascular Agents; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5