Erythropoietin production can be enhanced by normobaric oxygen breathing in healthy humans

Abstract

Erythropoietin (EPO) induces red blood cell production by activating red bone marrow progenitor cells, and is used therapeutically in chronic anemia. It is also used as an unauthorized adjunct to increase the oxygen transport capacity in the blood of athletes. Renal tissue hypoxia is the only widely accepted trigger for EPO production (1-3), even if new oxygen-sensitive sites have been recently proposed (4-6). This is well established in models of reduced-oxygen delivery during anemia (7), reduced renal perfusion (8), or hypobaric or normobaric hypoxia (9, 10) or hypoxemia. In one report, hemoconcentration, following sporting activities (11), has been reported to increase EPO secretion. There does not seem to be agreement on the existence of a circadian variation in EPO secretion (12, 13), although the exact timing and magnitude of the nadir and zenith are not unequivocally established, nor is the EPO plasma concentration. Previous experiments in breath-hold divers have led us to hypothesize that another triggering mechanism might exist, independent from renal tissue hypoxia. After a series of deep breath-hold dives, two out of five divers showed a marked augmentation of serum EPO levels. During descent to depth, intra-alveolar oxygen tensions increase. During ascent from depth, oxygen tension falls to atmospheric values. During these (unpublished) experiments, no severe alveolar hypoxia was observed after surfacing, although EPO production seemed to increase. Recently, a Spanish study reported that short exposure to intermittent hypobaric hypoxia increased EPO production (14). We hypothesize that a sudden decrease in tissue-oxygen tension from hyperoxia back to normoxia might act as a trigger for EPO release.