(Journal of Cardiovascular Pharmacology and Therapeutics, Mar 2011; 16: 87 – 95) Losartan Decreases Cardiac Muscle Fibrosis and Improves Cardiac function in Dystrophin-Deficient Mdx Mice
Christopher F. Spurney, Arpana Sali, Alfredo D. Guerron, Micaela Iantorno, Qing Yu, Heather Gordish-Dressman, Sree Rayavarapu, Jack van der Meulen, Eric P. Hoffman, and Kanneboyina Nagaraju – USA
Recent experiments showed that long-term management of losartan, an angiotensin II type I receptor antagonist, enhanced 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 equals 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 volume echocardiography and skeletal muscle function was assessed utilizing grip potency testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed utilizing picrosirius red-colored staining and picture J analysis. Gene expression was evaluated utilizing real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was appreciably reduced in untreated (26.9% ± 3.5%) mice when compared with losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was appreciably decreased in losartan-treated mice (56 ± six vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was appreciably decreased in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscle tissue when compared with untreated mdx mice. There were no substantial distinctions in skeletal muscle function in between treated and untreated groups. long-term treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice.