Carbamylated erythropoietin enhances mice ventilatory responses to changes in O2 but not CO2 levels.
Erythropoietin (EPO) has beneficial tissue-protective effects in several diseases but erythrocytosis may cause deleterious effects in EPO-treated patients. Thus carbamylated-EPO (C-EPO) and other derivatives retaining tissue-protective but lacking bone marrow-stimulating actions have been developed. Although EPO modulates ventilatory responses, the effects of C-EPO on ventilation have not been investigated. Here, basal breathing and respiratory chemoreflexes were measured by plethysmography after acute and chronic treatments with recombinant human C-EPO (rhC-EPO; 15,000 IU/kg during 5days) or saline (control group). Hematocrit, plasma and brainstem rhC-EPO levels were also quantified. Chronic rhC-EPO significantly elevated tissue rhC-EPO levels but not hematocrit. None of the drug regimen altered basal ventilation (normoxia). Chronic but not acute rhC-EPO enhanced hyperoxic ventilatory depression, and sustained the hypoxic ventilatory response mainly via a reduction of the roll-off phase. By contrast, rhC-EPO did not blunt the ventilatory response to hypercapnia. Thus, chronic C-EPO may be a promising therapy to improve breathing during hypoxia while minimizing adverse effects on cardiovascular function.
Aix Marseille Univ, CNRS, CRN2M, Marseille, France.
Hanan
H
Khemiri
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France.
Marc
M
Maresca
Aix Marseille Univ, CNRS, CRN2M, Marseille, France. Electronic address: christian.gestreau@univ-amu.fr.
Christian
C
Gestreau
D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006400:Hematocrit / Q000379:methods; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000097:blood*; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
C488171:carbamylated erythropoietin; D004921:Erythropoietin; D002245:Carbon Dioxide; D010100:Oxygen
Breathing; Carbamylated derivative; Chemoreflexes; Erythropoietin; Plethysmography