Chronic effects of losartan on the muscles and the serologic profiles of mdx mice.

Abstract

AIMS:

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.

MAIN 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.

KEY FINDINGS:

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.

SIGNIFICANCE:

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.

• Authors: Eun-Mi Lee, Dae-Yong Kim, Ah-Young Kim, Eun-Joo Lee, Sang-Hyeob Kim, Myeong-Mi Lee, Soo-Eun Sung, Jin-Kyu Park, Kyu-Shik Jeong
• Journal: Life sciences (Life Sci) Vol. 143 Pg. 35-42 (Dec 15 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 26497927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Biomarkers
• Transforming Growth Factor beta
• Losartan

Topics

• Administration, Oral
• Angiotensin II Type 1 Receptor Blockers (administration & dosage)
• Animals
• Biomarkers (blood)
• Losartan (administration & dosage)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Muscle, Skeletal (drug effects, metabolism)
• Muscular Dystrophy, Duchenne (blood, drug therapy)
• Transforming Growth Factor beta (blood)
• Treatment Outcome