Effects of sildenafil on the human response to acute hypoxia and exercise

High Alt Med Biol. 2005 Spring;6(1):43-9. doi: 10.1089/ham.2005.6.43.


We examined the effects of the 5-phosphodiesterase (5-PDE) inhibitor sildenafil on pulmonary arterial pressure and some oxygen transport and cardiopulmonary parameters in humans during exposure to hypobaric hypoxia at rest and after exercise. In a double-blind study, 100 mg sildenafil or placebo was administered orally to 14 healthy volunteers 45 min before exposure to 5,000 m of simulated altitude. Arterial oxygen saturation (SaO2), heart rate (HR), tidal volume (VT), respiratory rate (RR), left ventricular ejection fraction (EF), and pulmonary arterial pressure (PAP) were measured first at rest in normoxia, at rest and immediately after exercise during hypoxia, and after exercise in normoxia. The increase in systolic PAP produced by hypoxia was significantly decreased by sildenafil at rest from 40.9 +/- 2.6 to 34.9 +/- 3.0 mmHg (-14.8%; p = 0.0046); after exercise, from 49.0 +/- 3.9 to 42.9 +/- 2.6 mmHg (-12.6%; p = 0.003). No significant changes were found in normoxia either at rest or after exercise. Measurements of the effect of sildenafil on exercise capacity during hypoxia did not provide conclusive data: a slight increase in SaO2 was observed with exercise during hypoxia, and sildenafil did not cause significant changes in ventilatory parameters under any condition. Sildenafil diminishes the pulmonary hypertension induced by acute exposure to hypobaric hypoxia at rest and after exercise. Further studies are needed to determine the benefit from this treatment and to further understand the effects of sildenafil on exercise capacity at altitude.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Altitude*
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Exercise Tolerance / drug effects
  • Exercise*
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Humans
  • Hypoxia / drug therapy*
  • Male
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / pharmacology*
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Pulmonary Artery / drug effects
  • Pulmonary Circulation / drug effects*
  • Purines
  • Reference Values
  • Sildenafil Citrate
  • Sulfones
  • Tidal Volume / drug effects
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*
  • Ventricular Function, Left / drug effects


  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate