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Title:	Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model
Author:	Gay Jordi, Gemma; Guasch i Casany, Eduard; Benito, Begoña; Brugada Terradellas, Josep, 1958-; Nattel, Stanley; Mont Girbau, Lluís; Serrano i Mollar, Anna
Notes:	Rationale Recently it has been shown that long-term intensive exercise practice is able to induce myocardial fibrosis in an animal model. Angiotensin II is a profibrotic hormone that could be involved in the cardiac remodeling resulting from endurance exercise. Objective This study examined the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in an animal model of heart fibrosis induced by long-term intense exercise. Methods and Results Male Wistar rats were randomly distributed into 4 experimental groups: Exercise, Exercise plus losartan, Sedentary and Sedentary plus losartan. Exercise groups were conditioned to run vigorously for 16 weeks. Losartan was orally administered daily before each training session (50 mg/kg/day). Time-matched sedentary rats served as controls. After euthanasia, heart hypertrophy was evaluated by histological studies; ventricular collagen deposition was quantified by histological and biochemical studies; and messenger RNA and protein expression of transforming growth factor-β1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I and procollagen-III was evaluated in all 4 cardiac chambers. Daily intensive exercise caused hypertrophy in the left ventricular heart wall and originated collagen deposition in the right ventricle. Additionally long-term intensive exercise induced a significant increase in messenger RNA expression and protein synthesis of the major fibrotic markers in both atria and in the right ventricle. Losartan treatment was able to reduce all increases in messenger RNA expression and protein levels caused by exercise, although it could not completely reverse the heart hypertrophy. Conclusions Losartan treatment prevents the heart fibrosis induced by endurance exercise in training animals.
Subject(s):	-Malalties cardiovasculars -Models animals en la investigació -Farmacologia cardiovascular -Cardiovascular diseases -Animal models in research -Cardiovascular pharmacology
Rights:	cc-by (c) Gay-Jordi, Gemma et al., 2013 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Public Library of Science (PLoS)
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