Losartan Decreases Cardiac Muscle Fibrosis and Improves Cardiac Function in Dystrophin-Deficient Mdx Mice
Open Access
- 8 February 2011
- journal article
- other
- Published by SAGE Publications in Journal of Cardiovascular Pharmacology and Therapeutics
- Vol. 16 (1), 87-95
- https://doi.org/10.1177/1074248410381757
Abstract
Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmdmdx/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice.Keywords
This publication has 33 references indexed in Scilit:
- Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient MousePLOS ONE, 2010
- Long‐term therapy with deflazacort decreases myocardial fibrosis in mdx miceMuscle & Nerve, 2009
- Contrasting effects of steroids and angiotensin‐converting‐enzyme inhibitors in a mouse model of dystrophin‐deficient cardiomyopathyEuropean Journal of Heart Failure, 2009
- Preclinical drug trials in the mdx mouse: Assessment of reliable and sensitive outcome measuresMuscle & Nerve, 2009
- Early manifestation of alteration in cardiac function in dystrophin deficient mdx mouse using 3D CMR taggingJournal of Cardiovascular Magnetic Resonance, 2009
- Angiotensin II Induces Inflammatory Response Partly Via Toll-Like Receptor 4-Dependent Signaling Pathway in Vascular Smooth Muscle CellsCellular Physiology and Biochemistry, 2009
- Non-Smad pathways in TGF-β signalingCell Research, 2008
- N-Acetylcysteine Abolishes the Protective Effect of Losartan Against Left Ventricular Remodeling in Cardiomyopathy HamsterAntioxidants and Redox Signaling, 2008
- Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heartNeuromuscular Disorders, 2008
- Modulation of disease severity in mice with targeted disruption of the acid α-glucosidase geneNeuromuscular Disorders, 2000