title: [Clinical use of phosphodiesterase-5 inhibitors in cardiopulmonary diseases: from experimental evidence to clinical application].
abstract: Phosphodiesterases are a class of proteins that primarily modulate intracellular levels of cyclic nucleotides such as cGMP and cAMP. Phosphodiesterase-5 (PDE5) is mainly involved in the smooth muscle cell cGMP inactivation. Chemical inhibition of PDE5 has recently become a valid therapeutic option of nitric oxide pathway potentiation via cell cGMP availability. More specifically, PDE5 inhibition appears successful for the treatment of idiopathic pulmonary arterial hypertension. Additional intriguing therapeutic properties are a protective effect on the myocardium through antihypertrophic and antiapoptotic mechanisms and on vascular function by improving endothelial responsiveness and tolerance to myocardial ischemia-reperfusion injury. These effects imply a potential usefulness in the treatment of coronary artery disease and heart failure. Evidence currently available for considering PDE5 inhibition an additional therapeutic opportunity in cardiovascular disorders is provided.
authors.affiliation: Unità Cardiopolmonare, Ospedale San Paolo, Università degli Studi, Milano. marco.guazzi@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Guazzi
authors.forename: Marco
authors.initials: M
authors.lastname: Vicenzi
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002243:Carbolines / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018849:Controlled Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D019157:Ischemic Preconditioning, Myocardial; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use; D000068581:Tadalafil; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020257:Ventricular Remodeling
chemical_list: D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5