INTRODUCTION S EA-LEVEL DWELLERS EXPOSED TO altitude hy- poxia exhibit pulmonary vasoconstriction and a secondary increase in pulmonary arter- ial pressure (PAP). Excessive pulmonary vaso- constriction due to hypoxia is considered one of the main causes of high altitude pulmonary edema (HAPE) (Bartsch, 1999; Hackett and Rennie, 2002; Hultgren, 1997; Swenson et al., 2002; Voelkel, 2002). Several studies have shown that vasodilatory drugs that lower PAP HIGH ALTITUDE MEDICINE & BIOLOGY Volume 6, Number 1, 2005 © Mary Ann Liebert, Inc. Effects of Sildenafil on the Human Response to Acute Hypoxia and Exercise ANTONI RICART, 1,3 JAUME MARISTANY, 1 NÚRIA FORT, 2 CONXITA LEAL, 3 TERESA PAGÉS, 2 and GINÉS VISCOR 2 ABSTRACT Ricart, Antoni, Jaume Maristany, Núria Fort, Conxita Leal, Teresa Pagés, and Ginés Viscor. Ef- fects of sildenafil on the human response to acute hypoxia and exercise. High Alt. Med. Biol. 6:43–49, 2005.—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 ex- posure to 5,000 m of simulated altitude. Arterial oxygen saturation (Sa O 2 ), heart rate (HR), tidal volume (VT), respiratory rate (RR), left ventricular ejection fraction (EF), and pulmonary arter- ial pressure (PAP) were measured first at rest in normoxia, at rest and immediately after exer- cise 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 Sa O 2 was observed with exercise during hypoxia, and sildenafil did not cause sig- nificant changes in ventilatory parameters under any condition. Sildenafil diminishes the pul- monary hypertension induced by acute exposure to hypobaric hypoxia at rest and after exer- cise. Further studies are needed to determine the benefit from this treatment and to further understand the effects of sildenafil on exercise capacity at altitude. Key Words: pulmonary hypertension; high altitude pulmonary edema; 5-phosphodiesterase; pul- monary vasoconstriction; high altitude; hypobaric chamber 1 Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. 2 Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. 3 Institut d’Estudis de Medicina de Muntanya, Barcelona, Spain. 43