title: Acute cardiac and hemodynamic effects of sildenafil on resistant hypertension.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our data suggest PDE5i acutely improves diastolic function and hemodynamic profile in RHTN subjects, despite unchanging endothelial dysfunction.
authors: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Clinic Hospital, University of Campinas (UNICAMP), FCM 10 Building, 1st Floor, Campinas, SP, Brazil, 13083-970, tquinaglia@yahoo.com.br.
authors: Thiago
authors: T
authors: Quinaglia
authors: Ana Paula C
authors: AP
authors: de Faria
authors: Vanessa
authors: V
authors: Fontana
authors: Natália R
authors: NR
authors: Barbaro
authors: Andréa R
authors: AR
authors: Sabbatini
authors: Jonas T
authors: JT
authors: Sertório
authors: Caroline
authors: C
authors: Demacq
authors: José E
authors: JE
authors: Tanus-Santos
authors: Heitor
authors: H
authors: Moreno
mesh_terms: D000368:Aged; D062186:Arterial Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009573:Nitrites / Q000097:blood; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D016037:Single-Blind Method; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D009573:Nitrites; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP
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