In this study, we examined the effects of 2-week hindlimb un-loading in mice followed by re-ambulation with voluntary access to running wheels. The recovery period was terminated at a time point when physical performance--defined by velocity, time, and distance ran per day--of the suspended group matched that of an unsuspended group. Mice were assigned to one of four groups: unsuspended non-exercise (Control), 14 days of hindlimb suspension (HS), 7 days of access to running wheels (E7), or 14 days of HS plus 7 days access to running wheels (HSE7). HS resulted in significant decreases in body and muscle mass, hindlimb strength, soleus force, soleus specific force, fatigue resistance, and fiber cross sectional area (CSA). Seven days of re-ambulation with access to running wheels following HS recovered masses to Control values, increased fiber CSA, increased resistance to fatigue and improved recovery from fatigue in the soleus. HS resulted in a myosin heavy chain (MHC) phenotype shift from slow toward fast-twitch fibers, though running alone did not influence the expression of MHC fibers. Compared to the Control group, HSE7 mice did not recover functional hindlimb strength as assessed through measurements either in vivo or ex vivo. Results from this study demonstrate that 7 days of muscle re-loading with access to wheel-running following HS can stimulate muscle to regain mass and fiber CSA and exhibit improved metrics of fatigue resistance and recovery, yet muscles remain impaired in regard to strength. Understanding this mismatch between muscle morphology and strength may prove of value in designing effective exercise protocols for disuse muscle atrophy rehabilitation.

The results demonstrate that HEFT is an effective tool for evaluating in vivo hindlimb neuromuscular performance due to disuse muscle atrophy and potentially for other disease and injury models.

\ m=-\ 1 (decrease to 33 \ m=+-\7% and 31 \ m=+-\ 5% of control culture values, respectively). Addition of LH to the media increased inhibitor activity 3.04 \ m=+-\ 0.39 times compared with the control; however, A23187 (10 and 100 \g=m\mol l\m=-\1 ), in the presence of LH, decreased inhibitor activity by approximately 67%. The ionophore had disparate effects on progesterone production. Without LH, A23187 increased progesterone production by 2.96 \ m=+-\ 0.47 times at 10 \g=m\mol l\m=-\1and by 5.53 \ m=+-\ 0.65 times at 100 \g=m\mol l \ m=-\ 1 . However, in LH-stimulated cells, progesterone was inhibited by A23187 at 1 and 10 \g=m\mol l\m=-\1but was unchanged at 100 \g=m\mol l \m=-\1. In the angiotensin experiment, addition of AII (0\p=n-\10 000 nmol l\m=-\1 ) or saralasin (1 \g=m\mol l\m=-\1 ) did not affect inhibitor activity or progesterone concentrations compared with control values in the absence or presence of LH. For the angiotensin experiment in vivo, PMSG-primed rats were injected with hCG followed by saralasin (10 mmol l \ m=-\ 1 ) 1 or 3 h later and killed at 4, 8, or 12 h after hCG. Expression of the ovarian tissue inhibitor of metalloproteinase-1 (TIMP-1) increased by 1.7 times at 4 h, 3.3 times at 8 h, and 3.0 times at 12 h after hCG compared with values in ovaries collected at the time of hCG injection. Administration of saralasin at 1 or 3 h after hCG had no effect on expression of TIMP-1 or on serum concentrations of progesterone or oestradiol. In summary, A23187 decreased granulosa cell-derived inhibitor activity, whereas AII had no effect. We propose that calcium may play a role in modulating proteolysis associated with ovulation, while AII does not appear to regulate ovarian metalloproteinase inhibitor activity.

No abstract