Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Area of Science:

• Pulmonary physiology
• Altitude medicine
• Pharmacology

Background:

• Lung diffusing capacity varies in high-altitude newcomers, potentially linked to pulmonary vascular resistance (PVR).
• Understanding these adaptations is crucial for managing health at extreme altitudes.

Purpose of the Study:

• To investigate the effects of sitaxsentan, an endothelin A receptor blocker, on lung diffusing capacity and exercise capacity in healthy volunteers at high altitude.
• To explore the relationship between PVR, lung diffusion, and exercise performance.

Main Methods:

• Twenty-two healthy volunteers underwent assessments at sea level and 5,050 m.
• Participants received either sitaxsentan (100 mg/day) or placebo for 1 week in a double-blind, randomized manner.
• Pulmonary vascular resistance (PVR) was measured using Doppler echocardiography.
• Exercise capacity was assessed via maximal oxygen uptake (Vo(2 max)).
• Diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method, along with membrane diffusing capacity (Dm) and capillary volume (Vc).

Main Results:

• Altitude exposure did not change DL(CO), DL(NO), or Dm but slightly decreased Vc.
• Exercise at altitude reduced DL(NO) and Dm.
• Sitaxsentan intake improved Vo(2 max) and increased resting and postexercise DL(NO) and Dm.
• Sitaxsentan-induced PVR reduction was inversely correlated with DL(NO).
• Both DL(CO) and DL(NO) correlated with Vo(2 max), with stronger correlations at altitude.

Conclusions:

• Pharmacological pulmonary vasodilation using sitaxsentan improves the membrane component of lung diffusion in high-altitude newcomers.
• This improvement in lung diffusion may contribute to enhanced exercise capacity at high altitudes.
• Sitaxsentan offers a potential therapeutic strategy for improving physiological adaptation to high-altitude environments.