Pulmonary artery pressure limits exercise capacity at high altitude.
Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day(-1) for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V'(O(2),max), by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V'(O(2),max) were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.
Naeije
R
R
Laboratory of Physiology, Faculty of Medicine, Free University, Brussels, Belgium. rnaeije@ulb.ac.be
Huez
S
S
Lamotte
M
M
Retailleau
K
K
Neupane
S
S
Abramowicz
D
D
Faoro
V
V
D000208:Acute Disease; D000328:Adult; D000531:Altitude; D001794:Blood Pressure / Q000502:physiology; D002908:Chronic Disease; D065130:Endothelin A Receptor Antagonists; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D007555:Isoxazoles / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D013876:Thiophenes / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D065130:Endothelin A Receptor Antagonists; D007555:Isoxazoles; D013876:Thiophenes; C106276:sitaxsentan