Marina Brito da Silva -  research conducted to get the Master of Science  in  Department of Surgery of the Sao Paulo University, Faculty of Veterinary Medicine and Animal Science, Sao Paulo, SP, Brazil under orientation of Maria Angelica Miglino.

 Duchenne Muscular Dystrophy (DMD) has the substitution of the muscle by connective tissue as its most relevant characteristic. Once fibrotic proliferation is a major obstacle to the efficacy of therapy for muscular dystrophies, early interventions to prevent it will probably be necessary as part of an effective treatment. A significant correlation between fibrosis and the expression of TGF-beta 1, a multifunctional cytokine, in Duchenne muscular Dystrophy has been reported, emphasizing the role of cytokine in the development of muscle fibrosis, and suggesting it as target for fibrosis therapies. In this study we evaluated the effect of losartan over the development of connective tissue on the skeletal musculature of the canine model GRMD. One dystrophic dog was previously used in the pilot study to estipulate the dosage and side effects caused by losartan. Five dystrophic dogs, two male and two female and one control animal were used in the experiment. A dose of 50mg of losartan was orally given once a day. The clinical and laboratorial exams did not show any adverse effect through the experimental period. Therefore losartan utilization showed to be safe therapy. Muscle biopsy fragments have been removed before starting losartan (T0) and after (Tf) were used for histology and TGF beta-1 imunohistochemistry to compare this two times. The evaluations range of motion and limb circunference measures within imunohistochemistry and collagen quantification results helped to infer about losartan effect in the dystrophyc muscle fibrosis. Range of motion and limb circumference values did not show statistical difference. Although the percentage of connective tissue deposition area in the animals in Tf was statistically lower lower than T0. The decrease of TGF beta-1 signalization showed in imunohystochimestry pictures within the decrease of connective tissue deposition, after losartan, suggest an inhibitory effect of this medication through this cytokine in the studied GRMD muscle.