AJP - Regulatory, Integrative and Comparative Physiology, Vol 258, Issue 3 678-R683, Copyright © 1990 by American Physiological Society
Triggering of erythropoietin production by hypoxia is inhibited by respiratory and metabolic acidosis
K. U. Eckardt, A. Kurtz and C. Bauer
Department of Physiology, University of Zurich, Switzerland.
Erythropoietin (EPO) production in response to hypoxic hypoxia is known to
be attenuated by simultaneous hypercapnia. This study aimed to investigate
whether this inhibitory effect of hypercapnia is 1) a direct effect of
carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also
carbon monoxide hypoxia, and 3) influences either the synthesis and release
of EPO or the mechanisms by which hypoxia triggers an increase in EPO
production rate. We found that EPO formation in mice exposed to normobaric
hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when
animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38%
when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected
to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15
min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO
levels when initiated after the hypoxic period. The results indicate that
acidosis inhibits hypoxia-induced triggering of EPO formation independently
of PCO2 and HCO3 levels. Because this inhibitory effect is also present
during carbon monoxide hypoxia, it appears not solely due to potentiated
hyperpnea. Alternatively, it may result from a facilitated intrarenal
oxygen release or a direct effect at the EPO production sites.
