Acute high-altitude exposure profoundly influences oxygen availability, requiring a rapid and sustained adaptation of multiple organ systems, including the respiratory system and the pulmonary vasculature. Depending on the degree of hypoxia and the duration of stay, one of the most important factors in the acclimatization of lowlanders to high altitude is the progressive increase in ventilation, resulting in an increase in arterial PO2 and a decrease in arterial PCO2 over hours to days and weeks. At the vascular level, the main initial pulmonary adaptive mechanism to high altitude is hypoxic pulmonary vasoconstriction (HPV), also known as the Euler–Liljestrand mechanism, which leads to an increase in pulmonary artery pressure and right ventricular afterload.