Heat stress attenuates skeletal muscle atrophy in hindlimbunweighted rats. J. Appl. Physiol. 88: 359-363, 2000.-This study tested the hypothesis that elevation of heat stress proteins by whole body hyperthermia is associated with a decrease in skeletal muscle atrophy induced by reduced contractile activity (i.e., hindlimb unweighting). Female adult rats (6 mo old) were assigned to one of four experimental groups (n ϭ 10/group): 1) sedentary control (Con), 2) heat stress (Heat), 3) hindlimb unweighting (HLU), or 4) heat stress before hindlimb unweighting (HeatϩHLU). Animals in the Heat and HeatϩHLU groups were exposed to 60 min of hyperthermia (colonic temperature ϳ41.6°C). Six hours after heat stress, both the HLU and HeatϩHLU groups were subjected to hindlimb unweighting for 8 days. After hindlimb unweighting, the animals were anesthetized, and the soleus muscles were removed, weighed, and analyzed for protein content and the relative levels of heat shock protein 72 (HSP72). Compared with control and HLU animals, the relative content of HSP72 in the soleus muscle was significantly elevated (P Ͻ 0.05) in both the Heat and HeatϩHLU animals. Although hindlimb unweighting resulted in muscle atrophy in both the HLU and HeatϩHLU animals, the loss of muscle weight and protein content was significantly less (P Ͻ 0.05) in the HeatϩHLU animals. These data demonstrate that heat stress before hindlimb unweighting can reduce the rate of disuse muscle atrophy. We postulate that HSP70 and/or other stress proteins play a role in the control of muscle atrophy induced by reduced contractile activity. non-weight bearing; hindlimb suspension; hyperthermia; heat shock protein 70; protein synthesis; soleus muscle IT IS WELL KNOWN THAT DECREASING the load on a skeletal muscle results in muscle atrophy (1,8,(14)(15)(16). Studies using a rodent model of muscle disuse atrophy (i.e., hindlimb unweighting via tail suspension) indicate that the initial loss of muscle protein is primarily due to a decrease in the rate of protein synthesis (14). Subsequent atrophy then occurs by increased rates of protein degradation (14). It has been suggested that the initial decrease in protein synthesis during non-weightbearing activity is a result of a reduced rate of nascent polypeptide chain elongation at the ribosomal level (7). Because the inducible form of the 70-kDa heat shock protein (HSP72) plays an important role in chaperoning nascent peptides during translation, it has been postulated that a decrease in cellular HSP72 levels in myocytes is a potential mechanism to explain the decreased translation observed during muscle disuse (8). Hence, it is conceivable that elevation of cellular HSP72 levels could serve as a countermeasure to attenuate the disuse-induced reduction in protein synthesis.It also seems possible that HSP72 can play a protective role in the prevention of muscle protein degradation during periods of reduced contractile activity. A conceivable link between HSP72 and reduced protein degradation in muscle is as follows. Recent evid...