High altitude training of dogs results in elevated erythropoietin and endothelin-1 serum levels.

Living at 2300-m altitude combined with intermittent training at 3500 m leads to cardiovascular alterations in dogs, including increase in systemic and pulmonary artery pressure. Despite moderate to marked hypoxemia at these altitudes, erythrocytosis does not develop. To study humoral mechanisms of acclimatisation to high altitude, erythropoietin (EPO), endothelin-1 (ET-1), big endothelin (Big-ET) and vascular endothelial growth factor (VEGF) were measured in dogs living at 2300 m and intermittently ascending to 3500 m, and compared to the values obtained in control dogs living at 700-900 m. While the median EPO and ET-1 level in dogs at 2300 m did not differ from the one measured at 700-900 m, exposure from 2300 to 3500 m resulted in significantly elevated EPO and ET-1 levels. Big-ET levels were significantly higher at 2300 and 3500 m compared to dogs at low altitude, but did not differ between 2300 and 3500 m. VEGF was significantly elevated in dogs at 2300 m compared to dogs at low altitude. The increases in EPO, VEGF, ET-1 and Big-ET are thought to reflect the effect of hypoxia on a cellular level in these dogs. Obviously, the mild elevation of EPO levels observed at 3500 m was not sufficient to cause erythrocytosis. Elevations of the vasoconstrictors Big-ET and ET-1 may play some, but not a central role in hypoxic vasoconstriction in these dogs. Finally, serum VEGF measurement may be a sensitive and useful test to assess hypoxic stress in dogs.