title: Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension.
abstract: OBJECTIVE
  Left ventricular hypertrophy and diastolic dysfunction (LVDD) remain highly frequent markers of cardiac damage and risk of progression to symptomatic heart failure, especially in resistant hypertension (RHTN). We have previously demonstrated that administration of sildenafil in hypertensive rats improves LVDD, restoring phosphodiesterase type 5 (PDE-5) inhibition in cardiac myocytes.
  
  
  METHODS
  We hypothesized that the long-acting PDE-5 inhibitor tadalafil may be clinically useful in improving LVDD in RHTN independently of blood pressure (BP) reduction. A single blinded, placebo-controlled, crossover study enrolled 19 patients with both RHTN and LVDD. Firstly, subjects received tadalafil (20 mg) for 14 days and after a 2-week washout period, they received placebo orally for 14 days. Patients were evaluated by office BP and ambulatory BP monitoring (ABPM), endothelial function (FMD), echocardiography, plasma brain natriuretic peptide (BNP-32), cyclic guanosine monophosphate (cGMP) and nitrite levels.
  
  
  RESULTS
  No significant differences were detected in BP measurements. Remarkably, at least four echocardiographic parameters related with diastolic function improved accompanied by decrease in BNP-32 in tadalafil use. Although increasing cGMP, tadalafil did not change endothelial function or nitrites. There were no changes in those parameters after placebo.
  
  
  CONCLUSIONS
  The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.
authors.affiliation: Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Santos
authors.forename: Ana Paula C
authors.initials: AP
authors.lastname: de Faria
authors.forename: Natália R
authors.initials: NR
authors.lastname: Barbaro
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Modolo
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Ferreira-Melo
authors.forename: José R
authors.initials: JR
authors.lastname: Matos-Souza
authors.forename: Otávio R
authors.initials: OR
authors.lastname: Coelho
authors.forename: Juan C
authors.initials: JC
authors.lastname: Yugar-Toledo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.forename: David
authors.initials: D
authors.lastname: Calhoun
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D003971:Diastole / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009573:Nitrites / Q000097:blood; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016037:Single-Blind Method; D000068581:Tadalafil; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002243:Carbolines; D009573:Nitrites; D058986:Phosphodiesterase 5 Inhibitors; D020097:Natriuretic Peptide, Brain; D000068581:Tadalafil; D006152:Cyclic GMP