European Journal of Clinical Pharmacology

, Volume 70, Issue 2, pp 147–154 | Cite as

Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension

  • Rodrigo C. Santos
  • Ana Paula C. de Faria
  • Natália R. Barbaro
  • Rodrigo Modolo
  • Silvia E. Ferreira-Melo
  • José R. Matos-Souza
  • Otávio R. Coelho
  • Juan C. Yugar-Toledo
  • Vanessa Fontana
  • David Calhoun
  • Heitor Moreno
Clinical Trial



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.


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.


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.


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.


Refractory hypertension PDE5-inhibitors Left ventricular diastolic function 



This study was supported by the State of São Paulo Research Foundation (Fapesp) and National Council for Scientific and Technological Development (CNPq), Brazil.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Rodrigo C. Santos
    • 1
  • Ana Paula C. de Faria
    • 1
  • Natália R. Barbaro
    • 1
  • Rodrigo Modolo
    • 1
  • Silvia E. Ferreira-Melo
    • 1
  • José R. Matos-Souza
    • 1
  • Otávio R. Coelho
    • 1
  • Juan C. Yugar-Toledo
    • 2
  • Vanessa Fontana
    • 1
  • David Calhoun
    • 3
  • Heitor Moreno
    • 1
    • 4
  1. 1.Faculty of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.State Medical School at São José do Rio Preto (FAMERP)São José do Rio PretoBrazil
  3. 3.Division of Cardiovascular Disease, Vascular Biology, and Hypertension ProgramUniversity of Alabama at BirminghanBirminghanUSA
  4. 4.Laboratory of Cardiovascular PharmacologyUniversity of CampinasCampinasBrazil

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