title: Improvement in lung diffusion by endothelin A receptor blockade at high altitude.
abstract: Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.
authors: Laboratory of Physiologic Adaptations to Physical Activities, UPRES EA 3813, Poitiers University, Poitiers, France.
authors: Claire
authors: C
authors: de Bisschop
authors: Jean-Benoit
authors: JB
authors: Martinot
authors: Gil
authors: G
authors: Leurquin-Sterk
authors: Vitalie
authors: V
authors: Faoro
authors: Hervé
authors: H
authors: Guénard
authors: Robert
authors: R
authors: Naeije
mesh_terms: D000328:Adult; D000531:Altitude; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects / Q000502:physiology*; D044022:Receptor, Endothelin A / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D065130:Endothelin A Receptor Antagonists; D007555:Isoxazoles; D044022:Receptor, Endothelin A; D013876:Thiophenes; C106276:sitaxsentan