In
heart failure, exertional
fatigue of skeletal muscles can occur. A transgenic mouse overexpressing
calsequestrin can be regarded as an animal model of
heart failure. The aims of the present study were to investigate, whether at the time of
cardiac failure the composition of fiber types of skeletal muscles was altered, what kind of alterations in glycolytic and oxidative
enzyme activities occurred in different muscle fiber types and whether these were affected by the administration of the
angiotensin II receptor blocker,
losartan. Hemodynamic parameters were determined using a working heart preparation. Four groups of mice were investigated: wild-type (WT) mice and transgenic (TG) mice overexpressing
calsequestrin, with and without
losartan treatment.
Enzyme activities were measured in homogenates of Rectus femoris muscle and in muscle fibers, which were typed by their metabolic profile.
Calcineurin expression was measured by Western blotting.
Succinate dehydrogenase activity was increased by 275% in R. femoris muscle homogenates of TG compared to WT mice. This was due to a 57% increase in slow oxidative fibers, which was accompanied by an increased
calcineurin expression in TG muscles. This increase was attenuated by
losartan treatment. With respect to glycerol-3-phosphate-dehydrogenase (GPDH), no difference was evident comparing WT and TG. Treatment with
losartan resulted in a down-regulation of GPDH in WT and TG. In conclusion, changes in skeletal muscles occur in this mouse model of
heart failure and these changes were antagonized by
losartan. In contrast to
heart failure patients, in the mouse model a shift to the oxidative phenotype of skeletal muscle was noted, possibly due to enhanced
calcineurin expression.