Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl(4)-Induced Skeletal Muscle Injury

TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl(4) intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl(4)-treatment group (n = 7), and CCl(4) + losartan treatment group (n = 7). After CCl(4) treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl(4) + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl(4) + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl(4) + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-β1 as a result of CCl(4)-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-β1 signaling.