Enhanced hypoxia-stimulated erythropoietin production in mice with depression of erythropoiesis induced by hyperoxia.
Current evidence suggests that a modulatory action on O(2)-dependent EPO secretion is exerted by the erythroid/precursor cell population in the erythropoietic organs through a negative feedback system. The hypothesis is based on studies of stimulated-EPO secretion performed in mice in whom the erythropoietic rates were either enhanced or depressed in the presence of normal plasma EPO half-lives. Since erythropoietic depression was elicited by cyclophosphamide administration, which could have altered EPO production directly, the aim of the present investigation was to estimate hypoxia-stimulated EPO secretion in a mouse model of functional depressed erythropoiesis induced by exposure to normobaric hyperoxia. Females CF#1 mice aged 70 d were divided into control (C) and experimental (E) groups. The former was maintained in plastic cages in a normal environment, while the latter was placed in an environment of 60% O(2)/40% N(2) in an 85-dm(3) atmospheric chamber with air flow of 1 L/min. Erythropoiesis was evaluated by either 24-h RBC-(59)Fe uptake or iron kinetics performed 3 h after IV injection of a tracer dose of (59)Fe. Both indexes of the red cell production rate were significantly depressed in E mice. Plasma disappearance of exogenous EPO in C mice, as well as in E mice exposed to hyperoxia for 4 d, was estimated by injecting (125)I-rHuEPO intravenously. Linear regression analysis indicated that neither the differences between the slopes of both curves nor the Y-intercepts were significant. Hypobaric hypoxemia was used as stimulus for EPO production. Plasma immuno-EPO titer after a 4-h exposure to hypobaric air was 73% higher in mice with hyperoxia-induced hypoerythropoiesis than in control mice with normal erythropoiesis. Data support the concept that the rate of erythropoiesis, perhaps through the number of the erythroid progenitor/precursor cell population, modulates O(2)-dependent EPO secretion.
Bozzini
Carlos E
CE
Department of Physiology, Faculty of Odontology, University of Buenos Aires, Argentina. cebozi@fisio.odon.uba.ar
Barceló
Ana C
AC
Conti
María I
MI
Martínez
María P
MP
Alippi
Rosa M
RM
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006400:Hematocrit; D018496:Hyperoxia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007504:Iron Radioisotopes; D016014:Linear Models; D051379:Mice; D023421:Models, Animal; D012044:Regression Analysis; D013154:Spleen / Q000378:metabolism
D007504:Iron Radioisotopes; D004921:Erythropoietin