title: Phosphodiesterase type 5 inhibition improves arterial stiffness after exercise but not exercise capacity in hypertensive men.
abstract: BACKGROUND
  Established hypertension is associated with abnormal exercise hemodynamics and reduced exercise capacity through mechanisms that may include contributions from arterial stiffness and endothelial vasomotor dysfunction. Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Recent studies suggest they may also be useful antihypertensive agents. We hypothesized they would reduce arterial stiffness and increase exercise capacity in hypertensive men.
  
  
  METHODS
  In a 3-way, randomized, placebo-controlled study, 15 untreated hypertensive and 15 matched normotensive male subjects received 50mg sildenafil (PDE5 inhibitor), 25mg hydralazine (control, cGMP-independent vasodilator) or placebo, 3 times daily for 1 week, and the effects on exercise blood pressure (during modest and maximal exercise), peak oxygen uptake, and arterial stiffness were investigated.
  
  
  RESULTS
  Peak oxygen uptake was significantly lower in hypertensive than normotensive subjects (analysis of variance [ANOVA] P < 0.0001), but not affected by sildenafil in either group. However, while pulse wave velocity, as a measure of arterial stiffness, increased after exercise in hypertensive men following placebo, sildenafil reversed these changes, significantly reducing pulse wave velocity compared with both placebo and hydralazine (ANOVA P = 0.0001).
  
  
  CONCLUSIONS
  PDE5 inhibition with sildenafil did not improve exercise capacity in hypertensive men. Nevertheless, our findings suggest that sildenafil may reduce arterial stiffness in the recovery period after exercise.
authors: Clinical Pharmacology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK.
authors: Teresa M
authors: TM
authors: Attinà
authors: Iain D
authors: ID
authors: Drummond
authors: Lorenzo S
authors: LS
authors: Malatino
authors: Simon R
authors: SR
authors: Maxwell
authors: David J
authors: DJ
authors: Webb
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D015444:Exercise / Q000502:physiology; D017079:Exercise Tolerance / Q000187:drug effects*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D063177:Pulse Wave Analysis; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D006830:Hydralazine; D000068677:Sildenafil Citrate