Slow- and fast-twitch hindlimb skeletal muscle phenotypes 12 wk after ⅚ nephrectomy in Wistar rats of both sexes

Abstract

This study describes fiber-type adaptations in hindlimb muscles, the interaction of sex, and the role of hypoxia on this response in 12-wk ⅚ nephrectomized rats (Nx). Contractile, metabolic, and morphological features of muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of Nx rats, and compared with sham-operated controls. Rats of both sexes were considered in both groups. A slow-to-fast fiber-type transformation occurred in the tibialis cranialis of Nx rats, particularly in males. This adaptation was accomplished by impaired oxidative capacity and capillarity, increased glycolytic capacity, and no changes in size and nuclear density of muscle fiber types. An oxidative-to-glycolytic metabolic transformation was also found in the soleus muscle of Nx rats. However, a modest fast-to-slow fiber-type transformation, fiber hypertrophy, and nuclear proliferation were observed in soleus muscle fibers of male, but not of female, Nx rats. Serum testosterone levels decreased by 50% in male but not in female Nx rats. Hypoxia-inducible factor-1α protein level decreased by 42% in the tibialis cranialis muscle of male Nx rats. These data demonstrate that 12 wk of Nx induces a muscle-specific adaptive response in which myofibers do not change (or enlarge minimally) in size and nuclear density, but acquire markedly different contractile and metabolic characteristics, which are accompanied by capillary rarefaction. Muscle function and sex play relevant roles in these adaptations.

High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats

“…Evidence of slow-to-fast fiber-type transition was observed in the TC muscle of uremic rats that did not receive exogenous calcitriol but not in uremic rats receiving calcitriol. This result suggests that vitamin D treatment counteracts the fiber-type switching in the direction I¡IIA¡IIX¡IIB reported in fasttwitch hindlimb muscles in the course of uremic myopathy (1,5,36,52). In a small uncontrolled study, it was reported an increase in the percentage of type IIA fibers accompanied by a reduction of type IIB fibers in muscle biopsies from elderly women treated with calcitriol and calcium for 3-6 mo (51).…”

“…Afterwards, rats were randomly allocated to the following groups with balanced sexes: sham-operated control (So; n ϭ 24) and 5/6 nephrectomy (Nx, n ϭ 36 rats). The Nx was carried out following a two-step procedure that reduces the original renal mass by five-sixths as previously described (1). The control So rats were sham operated with the same protocol and total duration of the surgery, except both kidneys were maintained intact.…”

“…1E). The specificity of these MAbs for MHC in rat skeletal muscle has previously been reported (1,27,48). The immunoperoxidase staining protocol with avidin-biotin complex (ABC) protocol was used as previously described (43).…”

“…The fibers in the selected area were classified according to their MHC content by means of visual examination of immunostainings of the five serial sections stained with the battery of anti-MHC MAbs as previously described (1). The reactivity of each individual muscle fiber in these five consecutive sections was judged as positive or negative by comparing the intensity of the reaction of neighboring fibers.…”

“…Changes in skeletal muscle performance parameters have been extensively described over the past 40 yr in both CKD patients (e.g., 5,11,13,14,16,34,45) and animal models of uremia (4,9,18,19,38,52), but the reported findings are not uniform. A recent study by the authors' group provided evidence that skeletal muscle cells change their proportions and metabolic and structural features 12 wk after 5/6 nephrectomy (Nx), a widely used animal model of uremia (1). This malleability was muscle specific, being of greater magnitude in the fast-twitch (normally inactive at rest) tibialis cranialis (TC) muscle than in the slow-twitch (primarily active at rest providing postural support) soleus (SOL) muscle.…”