Determinants of erythropoietin release in response to short-term hypobaric hypoxia.
We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.
Ge
Ri-Li
RL
Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, and University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75231, USA.
Witkowski
S
S
Zhang
Y
Y
Alfrey
C
C
Sivieri
M
M
Karlsen
T
T
Resaland
G K
GK
Harber
M
M
Stray-Gundersen
J
J
Levine
B D
BD
D000208:Acute Disease; D000328:Adult; D000531:Altitude; D001158:Arteries; D001274:Atmospheric Pressure; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000097:blood / Q000652:urine; D012079:Renal Circulation
D004921:Erythropoietin; D010100:Oxygen