Erythropoietin improves cardiac contractility in post-hypoxic mice.
Mice myocardia, in which plasma erythropoietin (EPO) concentrations were modified in response to different experimental conditions, were studied to evaluate contractility (dF/dt). CF1 mice were randomly separated into four main groups: group I, normocythaemic normoxic; group II-a, normocythaemic intermittently exposed to hypobaria for 72 h; group II-b, normocythaemic intermittently exposed to hypobaria for 3 weeks; group III, hypertransfused polycythaemic exposed to 72 h hypobaria; and group IV, hypertransfused polycythaemic maintained in normobaric air. Plasma EPO, contractile studies and binding assays were performed. The dF/dt was significantly higher in group II-a than in group I and group II-b; but in groups III and IV, the dF/dt was reduced. The toxic action of ouabain was reduced and delayed in its onset, accompanied by increased numbers of 3H-ouabain binding sites in group II-a. Contractility was positively correlated with plasma EPO (pEPO) in the different groups. Treating group I with recombinant human (rHu)-EPO enhanced contractility while treating group II-a with a monoclonal anti-EPO decreased the dF/dt. The inhibition of enzymatic pathway(s) known to participate in the cytokines signal transduction, decreased the basal dF/dt values on atria from group II-a and on group I atria treated with rHu-EPO. The results demonstrated: (1) a cardiac non-haematopoietic effect of EPO; (2) that mice in which the pEPO concentration increased showed improvement in contractility and in the therapeutic action of ouabain; and (3) it is possible that EPO may act as a cardioprotective agent by modulating the cardiac Na+-K+ pump.
Sterin-Borda
Leonor
L
Pharmacology Unit, zSchool of Dentistry, University of Buenos Aires, Marcelo T. de Alvear 2142-4o"B", 1122AAH, Buenos Aires, Argentina.
Barceló
Ana C
AC
Bozzini
Carlos E
CE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004921:Erythropoietin / Q000032:analysis / Q000276:immunology / Q000502:physiology* / Q000627:therapeutic use; D005260:Female; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000627:therapeutic use; D011994:Recombinant Proteins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D004921:Erythropoietin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase