Acute cardiac and hemodynamic effects of sildenafil on resistant hypertension

Failure to control blood pressure (BP) despite the use of three or more drugs characterizes resistant hypertension (RHTN). Impaired endothelial function is associated with this condition and phosphodiesterase-5 inhibitors (PDE5i)-inhibiting cGMP breakdown-reduce BP in RHTN patients. We hypothesized that acute administration of PDE5i could ameliorate hemodynamic, endothelial parameters and left ventricular diastolic function (LVDF) in RHTN patients. Also, an exploratory analysis was performed to assess the influence of the T-786C endothelial NO synthase polymorphism on those responses. Subjects (n = 26) underwent a 6-month clinical screening for RHTN diagnosis. Increasing doses of oral sildenafil were given at 30 min intervals (37.5, 50 and 100 mg) while continuous non-invasive hemodynamic measures were assessed. LVDF, flow mediated dilation (FMD), nitrite and cGMP levels were also determined. Mean arterial pressure and total peripheral resistance decreased in all patients (84.17 +/- 21.04 to 75 +/- 17.21 mmHg; 1149 +/- 459.7 to 1037 +/- 340 dyn.s/cm(-5), respectively). Likewise, sildenafil improved diastolic dysfunction parameters (Left atrial volume: 25 +/- 5.8 to 20 +/- 4.4; IVRT: 104 +/- 19.33 to 88 +/- 15.22; E/e' septal: 9.7 +/- 3.8 to 7.9 +/- 2.9; E/e' lateral: 7.7 +/- 3.4 to 6.4 +/- 3.2). No statistical changes were found in FMD, nitrite and cGMP with PDE5i. Our data suggest PDE5i acutely improves diastolic function and hemodynamic profile in RHTN subjects, despite unchanging endothelial dysfunction.