Losartan, an angiotensin II type 1 receptor blocker, exerts protective effect on soleus muscle atrophy in female rats. Thus, we aimed to examine the effect of losartan treatment on the recovery of atrophied soleus muscles. Female Wistar rats were subjected to hindlimb unloading for 7 d and then reloading for 7 d with either phosphate-buffered saline (PBS; n = 9) or losartan (40 mg/kg/day; n = 9). The soleus muscles were removed at rest (sedentary control [SED]; n = 9), after 7 d of hindlimb unloading (HU; n = 9), and after 7 d of reloading (HUR-PBS or HUR-LOS; n = 9 each). The absolute and relative weights, and fiber cross-sectional area (CSA) of the soleus muscles of rats in the HU group were significantly reduced as compared to those of the rats in the SED group at 7 d post-hindlimb unloading. Seven days of reloading significantly increased the muscle weights of rats in the HUR-PBS and HUR-LOS groups, with the recovery rate of the absolute muscle weight and type I fiber CSA being significantly higher in the HUR-LOS group (6.1% and 10.1%, respectively) than in the HUR-PBS group (4.7% and 5.2%, respectively) (p < 0.05). Moreover, the absolute and relative muscle weight in HUR-PBS were lower than SED; however, no significant difference was observed between the SED and HUR-LOS groups. CSAs of type I and IIa fiber were significantly higher in the HUR-LOS group than in the HU group. Losartan administration during reloading resulted in increased Smad1/5/8 and mTOR signaling and decreased Smad2/3 signaling and protein ubiquitination, facilitating the recovery of atrophied soleus muscle. Therefore, losartan administration-induced muscle recovery may partially be attributed to enhanced Smad1/5/8 and mTOR signaling activation, and reduced activation of canonical TGF-β signaling (Smad2/3) in the soleus muscle.
Keywords: Angiotensin receptor blocker; Hindlimb unweighting; Muscular atrophy; Reloading; TGF-β signaling.
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