Losartan treatment attenuates hindlimb unloading-induced atrophy in the soleus muscle of female rats via canonical TGF-β signaling

We investigated the protective effect of losartan, an angiotensin II type 1 receptor blocker, on soleus muscle atrophy. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed on days 1 and 7 for analysis. Females showed greater reductions in relative weight and myofiber cross-sectional area of the soleus muscle than males on day 7 post-hindlimb unloading. Losartan partially protected females against muscle atrophy. Activation of the canonical TGF-β signaling pathway, assessed via Smad2/3 phosphorylation, was lower in females following losartan treatment and associated with lower levels of protein ubiquitination after 1 (myofibril) and 7 (cytosol) days of unloading. However, no effect was observed in non-canonical TGF-β signaling (p44/p42 and p38 MAPK phosphorylation) in males or females during unloading. Our results suggest that losartan provides partial protection against hindlimb unloading-induced soleus muscle atrophy in female rats, possibly associated with decreased canonical TGF-β signaling.