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

• Published in: European journal of clinical pharmacology 2014-02, Vol.70 (2), p.147-154
• Main Authors: Santos, Rodrigo C., de Faria, Ana Paula C., Barbaro, Natália R., Modolo, Rodrigo, Ferreira-Melo, Silvia E., Matos-Souza, José R., Coelho, Otávio R., Yugar-Toledo, Juan C., Fontana, Vanessa, Calhoun, David, Moreno, Heitor
• Format: Article
• Language: English
• Subjects: Aged; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Carbolines - pharmacology; Carbolines - therapeutic use; Cardiovascular disease; Clinical Trial; Cross-Over Studies; Cyclic GMP - blood; Diastole - drug effects; Drug Resistance; Drug therapy; Female; Humans; Hypertension; Hypertension - blood; Hypertension - drug therapy; Hypertension - physiopathology; Hypertrophy, Left Ventricular - blood; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - physiopathology; Male; Middle Aged; Natriuretic Peptide, Brain - blood; Nitrites - blood; Pharmacology; Pharmacology/Toxicology; Phosphodiesterase 5 Inhibitors - pharmacology; Phosphodiesterase 5 Inhibitors - therapeutic use; Single-Blind Method; Tadalafil; Ventricular Dysfunction, Left - blood; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - physiopathology; Ventricular Function, Left - drug effects
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-013-1611-8

Purpose 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. Conclusion 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.