Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

Background: Heart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. Methods and Results: We employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFkB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. Conclusions: Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state

Perfil nutricional e cardiovascular de ratos normotensos e hipertensos sob dieta hiperlipídica

FUNDAMENTO: Embora dietas hiperlipídicas (DH) promovam distúrbios nutricionais e cardíacos, poucos estudos avaliaram sua influência em ratos normotensos Wistar-Kyoto (WKY) e espontaneamente hipertensos (SHR). OBJETIVO: Avaliar e comparar o perfil nutricional e cardiovascular de WKY e SHR tratados com DH. MÉTODOS: 20 WKY e 20 SHR foram distribuídos em quatro grupos: WKY-controle (WKY-C), WKY-DH, SHR-controle (SHR- C) e SHR-DH. Os grupos C e DH receberam, respectivamente, dieta normocalórica e DH durante 20 semanas. Foram avaliados: peso corporal (PC), adiposidade, glicemia, lípides séricos, com dosagens de colesterol total e triacilglicerol, insulina e leptina. O estudo cardiovascular contemplou a pressão arterial sistólica (PAS), avaliação cardiopulmonar anatômica, ecocardiograma e histologia cardíaca. RESULTADOS: Os SHRs apresentaram menor PC, adiposidade, glicose, colesterol, triacilglicerol, leptina e insulina, quando comparados aos WKYs. Nos SHR, a ingestão calórica aumentou com a DH. Já nos WKYs, a DH elevou a eficiência energética, a adiposidade e a leptina e reduziu a glicemia. Na avaliação cardiovascular, os SHR apresentaram maior PAS, umidade pulmonar, hipertrofia e fibrose intersticial miocárdica em relação aos WKYs (p<0,01); mas a função cardíaca foi similar entre as cepas. A DH reduziu o diâmetro sistólico ventricular nos WKY e acentuou a relação E/A mitral, as espessuras diastólicas do septo interventricular e da parede posterior bem como a fibrose intersticial do ventrículo esquerdo. CONCLUSÃO: Embora não tenha afetado significativamente o perfil nutricional dos SHRs, o tratamento acentuou a remodelação cardíaca e precipitou o aparecimento de disfunção diastólica ventricular. Nos WKY, a dieta aumentou a adiposidade e a leptinemia, e promoveu modificações cardiovasculares não significantes.FUNDAMENTO: Embora dietas hiperlipídicas (DH) promovam distúrbios nutricionais e cardíacos, poucos estudos avaliaram sua influência em ratos normotensos Wistar-Kyoto (WKY) e espontaneamente hipertensos (SHR). OBJETIVO: Evaluar y comparar el perfil nutricional y cardiovascular de WKY y SHR tratadas con DH. MÉTODOS: Un total de 20 WKY y 20 SHR se distribuyó en cuatro grupos: WKY-control (WKY-C), WKY-DH, SHR-control (SHR-C) y SHR-DH. Los grupos C y DH recibieron, respectivamente, dieta normocalórica y DH durante 20 semanas. Se evaluaron: peso corporal (PC), adiposidad, glucemia, lípidos séricos, con dosificaciones de colesterol total y triacilglicerol, insulina y leptina. El estudio cardiovascular contempló la presión arterial sistólica (PAS), evaluación cardiopulmonar anatómica, ecocardiograma e histología cardiaca. RESULTADOS: Las SHRs presentaron menor PC, adiposidad, glucosa, colesterol, triacilglicerol, leptina e insulina, cuando comparadas a las WKYs. En las SHR, la ingestión calórica aumentó con la DH. Sin embargo en las WKYs, la DH elevó la efiCiência energética, la adiposidad y la leptina y reduzco la glucemia. En la evaluación cardiovascular, las SHR presentaron mayor PAS, humedad pulmonar, hipertrofia y fibrosis intersticial miocárdica en cuanto a las WKYs (p<0,01); sin embargo la función cardiaca se halló similar entre las cepas. La DH reduzco el diámetro sistólico ventricular en los WKY y acentuó la relación E/A mitral, los espesores diastólicos del septo interventricular y de la pared posterior así como la fibrosis intersticial del ventrículo izquierdo. CONCLUSIÓN: Aunque no afectó significativamente el perfil nutricional de las SHRs, el tratamiento acentuó la remodelación cardiaca y precipitó el aparecimiento de disfunción diastólica ventricular. En los WKY, la dieta aumentó la adiposidad y la leptinemia, y promovió modificaciones cardiovasculares no significantes.BACKGROUND: Although a high fat diet (HFD) promotes nutritional and heart disorders, few studies have assessed its influence in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). OBJECTIVE: To evaluate and compare the nutritional and cardiovascular profiles of WKY and SHR on a high fat diet. METHODS: 20 WKY and 20 SHR were divided into four groups: Control-WKY (C-WKY), HFD-WKY, Control-SHR (C-SHR) and HFD-SHR. The C and HFD groups received, respectively, a normocaloric diet and a HFD for 20 weeks. The following features were evaluated: body weight (BW), adiposity, blood glucose, serum lipids, with measurements of total cholesterol and triacylglycerol levels, insulin and leptin. The cardiovascular study included the systolic blood pressure (SBP), a cardiopulmonary anatomical evaluation, an echocardiography and heart histology. RESULTS: The SHR had BW, adiposity, glucose, cholesterol, triacylglycerol, leptin and insulin levels lower than the WKY. In SHR, the caloric intake increased with HFD. In WKY, the HFD increased energy efficiency, adiposity and blood leptin, and reduced glucose. In the cardiovascular assessment, the SHR had SBP, pulmonary moisture, myocardial hypertrophy and interstitial fibrosis higher than the WKY (p <0.01); the cardiac function was similar in both strains. The HFD reduced the ventricular systolic diameter in the WKY and increased the mitral E/A ratio, the diastolic thickness of the interventricular septum and the posterior wall, as well as the interstitial fibrosis of the left ventricle. (Arq Bras Cardiol 2009; 93(5) : 487-494) CONCLUSION: Although it had not significantly affected the nutritional profile of the SHR, the treatment increased cardiac remodeling and precipitated the emergence of ventricular diastolic dysfunction. In WKY, the diet increased adiposity and leptinemia, and promoted non-significant cardiovascular changes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

N-Acetylcysteine Influence on Oxidative Stress and Cardiac Remodeling in Rats During Transition from Compensated Left Ventricular Hypertrophy to Heart Failure

Background/Aims: To evaluate the effects of the antioxidant N-acetylcysteine (NAC) on cardiac structure and function in rats with long-term ascending aortic stenosis (AS). Methods: Four months after inducing AS, Wistar rats were assigned into the groups Sham, AS, and AS treated with NAC (AS-NAC) and followed for eight weeks. Cardiac structure and function were evaluated by echocardiogram. Myocardial antioxidant enzymes activity was measured by spectrophotometry and malondialdehyde serum concentration by HPLC. Gene expression of NADPH oxidase subunits NOX2, NOX4, p22 phox, and p47 phox was assessed by real time RT-PCR and protein expression of MAPK proteins by Western blot. Statistical analyzes were performed with Goodman and ANOVA or Mann-Whitney Results: NAC restored myocardial total glutathione (Sham 20.8±3.00; AS 12.6±2.92; AS-NAC 17.6±2.45 nmol/g tissue; p&#x3c;0.05 AS vs Sham and AS-NAC). Malondialdehyde serum concentration was lower in AS-NAC and myocardial lipid hydroperoxide was higher in AS (Sham 199±48.1; AS 301±36.0; AS-NAC 181±41.3 nmol/g tissue). Glutathione peroxidase activity was lower in AS than Sham. Echocardiogram showed LV concentric hypertrophy with systolic and diastolic dysfunction before and after treatment; no differences were observed between AS-NAC and AS groups. NAC reduced p-ERK and p-JNK protein expression, attenuated myocardial fibrosis, and decreased the frequency of right ventricular hypertrophy. Conclusion: N-acetylcysteine restores myocardial total glutathione, reduces systemic and myocardial oxidative stress, improves MAPK signaling, and attenuates myocardial fibrosis in aortic stenosis rats

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR). Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer). Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004). Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg). Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats

Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats

Background: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). Methods and Results: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR-C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.85±0.68; SHR-C 5.22±1.64; SHR-SPR 6.80±1.49 g/mm2; -dT/dt: WKY 18.0 (16.0-19.0); SHR-C 20.8 (18.4-25.1); SHR-SPR 28.9 (24.2-34.6) g/mm2/s]. Cardiomyocyte cross-sectional area and total collagen concentration (WKY 1.06±0.34; SHR-C 1.85±0.63; SHR-SPR 1.28±0.39 µg/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. Conclusion: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats