We hypothesized that muscle afferents activation by fatigue may trigger a spread out activation of heat shock proteins (HSP) in resting muscles and different organs. In anesthetized rats, HSP25 and HSP70 levels were determined in both tibialis anterior (TA) and extensor digitorum longus (EDL) muscles, diaphragm, kidney, and brain using ELISA kits, which mostly explore the phosphorylated HSP, and Western blotting (WB). One TA muscle was electrically stimulated and tissues sampled 10 (Test10) or 60 min (Test60) after the stimulation had ended. The nerve supply to the stimulated TA or its pair in the contralateral limb was left intact or suppressed. In control rats, no muscle stimulation was performed and tissues were sampled at the same time (C10 and C60). After TA stimulation, ELISA measured increased HSP25 content in contralateral TA, EDL, and diaphragm at Test 10 but not Test 60, and HSP70 increased in all sampled tissues at Test60. WB did not measure HSP25 and HSP70 variations at Test 10 while at Test 60 HSP25 increased in all sampled tissues except the brain and HSP70 was elevated in all tissues. Denervation of the contralateral non stimulated limb suppressed HSP variations in TA and after denervation of the stimulated TA the spread out activation of HSPs in other organ was absent. Our data suggest that fatigue-induced activation of skeletal muscle afferents triggers an early increase in phosphorylated HSP25 in muscles and a delayed elevation of non phosphorylated HSP25 and HSP70 in skeletal and respiratory muscles, kidney, and brain.

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