Chronic effects of losartan on the muscles and the serologic profiles of mdx mice.
OBJECTIVE
Losartan, an angiotensin II type 1 receptor blocker, attenuates transforming growth factor-β (TGF-β) signaling, which inhibits myogenic regeneration. Although many researchers have demonstrated that losartan has anti-fibrotic and protective effects on cardiac and skeletal muscles, for long-term administration to treat dystrophic disorders, it is essential to demonstrate not only the therapeutic effects of losartan on muscles but also its effects on other organs and on blood biochemistry.


METHODS
Mdx mice, an animal model of Duchenne muscular dystrophy (DMD), were fed losartan dissolved in tap water. After 44weeks, the skeletal (gastrocnemius), cardiac, and diaphragm muscles of mdx mice were removed. Tissue and blood samples were collected from all experimental animals. Effects of losartan on muscle regeneration, fibrosis, and blood enzymatic profiles were evaluated.


RESULTS
In histopathological findings and serum biochemistry analyses, chronic losartan administration showed muscular protective effects and inhibited fibrosis in skeletal (gastrocnemius), cardiac, and diaphragmatic muscles. In addition, losartan had no effects on other solid organs. Interestingly, losartan had beneficial effects on serum HDL ratio.


CONCLUSIONS
This study demonstrates the therapeutic effects of losartan on muscles and its effects on other organs and on blood biochemistry. In conclusion, our results provide useful information for consideration of chronic losartan administration be as a treatment of DMD.
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea.
Eun-Mi
EM
Lee
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Dae-Yong
DY
Kim
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea.
Ah-Young
AY
Kim
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea.
Eun-Joo
EJ
Lee
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Sang-Hyeob
SH
Kim
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Myeong-Mi
MM
Lee
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Soo-Eun
SE
Sung
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Jin-Kyu
JK
Park
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: jeongks@knu.ac.kr.
Kyu-Shik
KS
Jeong
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000188:drug therapy; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D016212:Transforming Growth Factor beta; D019808:Losartan
Anti-fibrotic effects; Chronic administration; Losartan; Muscle protective effects; Serologic profiles; mdx mice