Hypoxia-stimulated erythropoietin production in mice with hyperoxia-depressed erythropoiesis

Abstract

A great deal of evidence supports the concept that plasma erythropoietin levels (pEPO) in mammals are related to the O2 supply to tissues relative to their O2 needs. Current evidence also suggests that a modulatory action on O2-dependent EPO secretion is exerted by the erythroid progenitor/precursor cell populations in the erythropoietic organs through a negative feedback system. In this sense, enhanced EPO response to acute hypoxemia has been observed in our laboratory in mice with either pharmacological or post-hypoxic depression of erythropoiesis. The aim of the present investigation was to estimate hypoxia-stimulated EPO production in mice with hyperoxia-depressed red cell production. Female CF#1 mice aged 70d were divided in control (C) and experimental (E) groups. The former was maintained in plastic cages in a normal environments, while the latter was placed in an environment of 60%O2-40%N2. in an 85 dm3-atmosphere chamber with an air flow of 1 L/min. Carbon dioxide was removed from the chamber by washout and absorption with calcium hydroxide. Erythropoiesis was evaluated in 10 C and E mice by iron kinetics performed 3 h after i.v. injection of a tracer dose of 59Fe. The fraction of iron going to erythroid tissue (Hogdson test) was 65.7 % (p<0.0001) lower in E than in C mice, showing the erythropoiesis-lowering effect of hyperoxia after a 72-hour exposure. Hematocrit values were similar in both groups. O2-dependent EPO production was derived from pEPO (ELISA, Medac Diagnostika, Germany) changes after a 4-hour exposure to 506 mb in a decompression chamber. Plasma EPO was 173.2 % higher (p<0.05) in E than in C mice. Data support the concept that the rate of erythropoiesis modulates O2-dependent EPO secretion.