Does K-11706 Enhance Performance and Why?

Abstract

Erythropoietin gene expression is stimulated by hypoxia-inducible factor 1 and inhibited by GATA. Thus, drugs that attenuate the action of GATA and/or potentiate the action of HIF-1 may increase Epo production and hemoglobin concentration. The effects of such drugs on endurance performance and the potential mechanisms by which they may exert effects are unclear. In Hep3B cells, we showed that K-11706 inhibits GATA binding activity, but enhances HIF-1 binding activity. However, the expression levels of GATA and HIF-1 protein were not changed by the addition of K-11706. We investigated the effects of K-11706 on Epo and Hb concentrations, hematocrit and endurance performance of mice (total number of mice = 40). K-11706 was dissolved in polyethylene glycol and administered via oral tube feeding to mice for either five or eight days. Endurance performance was assessed using a treadmill. Muscle fibers from the quadriceps muscles of mice were stained with ATPase. Administration of 3 mg/kg K-11706 for five or eight days significantly increased erythropoietin concentrations, hemoglobin concentrations, hematocrit and endurance performance, but the diameters of cross-sections and ratios of type I, IIA and IIB muscle fibers were not affected.